Adrenal cortical carcinoma in children: a clinicopathological analysis of 25 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

Immunofluorescence Analysis of Estrogen and Progesterone Receptors and Ki-67 Nuclear Protein in Canine Uteri Treated with Medroxyprogesterone Acetate During Anestrus / Análisis de Inmunofluorescencia de Receptores de Estrógeno y Progesterona y Proteína Nuclear Ki-67 en Úteros Caninos Tratados con Acetato de Medroxiprogesterona Durante el Anestr

SUMMARY: Estradiol and progesterone receptors play an essential role in the changes occurring in the uterus during the estrus cycle in dogs (Canis lupus familiaris). In order to investigate the potential effect of progestational agent medroxyprogesterone acetate (MPA) when is used during anestrus on the expression of estradiol receptors [ER], progesterone receptors [PR] and nuclear protein Ki67, we evaluated uterine tissue immunohistochemically. Uteri were grouped as nulliparous (control, n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount and location of PR, ER and Ki67 were studied on the epithelial surface, apical and basal regions of the endometrium and myometrium using immunohistochemical techniques with a spectral confocal microscope and analyzed by ANOVA. Differences in ER were observed between the multiparous and MPA-treated groups in the apical region of the endometrium (p=0.0022). Differences in cell proliferation were detected between the nulliparous and multiparous groups (p=0.0037) and nulliparous and MPA-treated groups (p=0.0003) in the basal region of the endometrium. In conclusion, two doses of MPA (5mg/kg; i.m.) do not have a significant effect on the expression of ER and PR; however, they inhibit cell proliferation in the basal region of the endometrium, which includes the stroma, subepithelial cell layer, compact layer, and spongy layer. The clinical and long-term effect of this treatment should be evaluated in subsequent studies.

Los receptores de estradiol y progesterona juegan un rol fundamental en los cambios que se producen en el útero durante el ciclo estral de las perras (Canis lupus familiaris). El objetivo de este estudio fue evaluar las expresiones de ER-a y PR en el útero y la proliferación de células endometriales detectando la expresión nuclear de la proteína Ki67 en perras expuestas a la progestina sintética MPA y compararlas con perras nulíparas y multíparas expuestas a progesterona luteal. Úteros fueron agrupados como nulíparas (control, n=11), multíparas (n=11) y tratadas con MPA (n=11; nulíparas con dos tratamientos; 5 mg/kg; i.m.). La expresión de PR, ER-a y Ki67 fue evaluada en la regiones apicales y basales del endometrio y miometrio con un microscopio confocal espectral. Se observó diferencias en ER-a entre los grupos multíparas y tratados con MPA en la región apical del endometrio (p=0,0022). Se detectaron diferencias en la proliferación celular entre los grupos de nulíparas y multíparas (p=0,0037) y los grupos de nulíparas y tratados con MPA (p=0,0003) en la región basal del endometrio. En conclusión, dos dosis de MPA (5mg/kg; i.m.) no tienen un efecto significativo sobre la expresión de ER y PR; sin embargo, inhiben la proliferación celular en la región basal del endometrio, el cual incluye a estroma, capa de células subepiteliales, estratos compacto y esponjoso. El efecto clínico a largo plazo de este tratamiento debe ser evaluado en estudios posteriores.

Efetividade da marcação combinada de p16 e ki67 na referência de mulheres com citologia ASC-US ou LSIL para colposcopia / Effectiveness of combined p16 and ki67 labeling in the referral of women with ASC-US or LSIL cytology for colposcopy

Objetivo: Analisar o desempenho do teste de Dupla Marcação (DM) por p16 e Ki67 em amostras de células cervicais para detecção de lesões precursoras do câncer do colo do útero, comparando-o à repetição imediata da citologia em mulheres com resultado de citologia de rastreamento ASC-US ou LSIL. Metodologia: Trata-se de um estudo transversal que recrutou 121 mulheres nas unidades de Atenção Primária de Saúde dos municípios de Palmas e Porto Nacional, em Tocantins, e da cidade do Rio de Janeiro, com citologia de rastreamento com resultado ASC-US ou LSIL. As mulheres foram referidas aos Serviços de Referência do Colo participantes em Tocantins e no Rio de Janeiro. As participantes realizaram o exame de colposcopia e coleta de espécime para Citologia em Meio Líquido (CML) e para DM para p16 e Ki67. Os resultados dos testes foram comparados ao padrão-ouro misto definido pela colposcopia, histologia (quando obtido espécime histológico) na avaliação inicial, ou citologia, colposcopia e histologia (quando obtido espécime histológico) no seguimento de pelo menos 12 meses, definindo as que tinham lesão precursora (NIC II ou NIC III) ou não. Resultados: Das 121 mulheres recrutadas, 76 mulheres foram consideradas para esta análise por terem pelo menos um exame de triagem realizado (CML ou DM por p16-Ki67) e conclusão diagnóstica. Dessas, 42 apresentavam exame prévio de ASC-US e 34 de LSIL. A maioria (86,8%) estava na faixa etária recomendada para o rastreamento (25 a 64 anos). Objetivo: Analisar o desempenho do teste de Dupla Marcação (DM) por p16 e Ki67 em amostras de células cervicais para detecção de lesões precursoras do câncer do colo do útero, comparando-o à repetição imediata da citologia em mulheres com resultado de citologia de rastreamento ASC-US ou LSIL. Metodologia: Trata-se de um estudo transversal que recrutou 121 mulheres nas unidades de Atenção Primária de Saúde dos municípios de Palmas e Porto Nacional, em Tocantins, e da cidade do Rio de Janeiro, com citologia de rastreamento com resultado ASC-US ou LSIL. As mulheres foram referidas aos Serviços de Referência do Colo participantes em Tocantins e no Rio de Janeiro. As participantes realizaram o exame de colposcopia e coleta de espécime para Citologia em Meio Líquido (CML) e para DM para p16 e Ki67. Os resultados dos testes foram comparados ao padrão-ouro misto definido pela colposcopia, histologia (quando obtido espécime histológico) na avaliação inicial, ou citologia, colposcopia e histologia (quando obtido espécime histológico) no seguimento de pelo menos 12 meses, definindo as que tinham lesão precursora (NIC II ou NIC III) ou não. Resultados: Das 121 mulheres recrutadas, 76 mulheres foram consideradas para esta análise por terem pelo menos um exame de triagem realizado (CML ou DM por p16-Ki67) e conclusão diagnóstica. Dessas, 42 apresentavam exame prévio de ASC-US e 34 de LSIL. A maioria (86,8%) estava na faixa etária recomendada para o rastreamento (25 a 64 anos). Oito mulheres (10,5%) apresentaram NIC II ou III como conclusão diagnóstica. Verificou-se que o teste da DM de p16 e Ki67 identificou um número maior de mulheres com um desses diagnósticos, encaminhando 50% das mulheres com ASC-US ou LSIL na citologia de rastreamento para colposcopia, mas deixando de identificar 50% dessas mulheres. Esse teste mostrou-se 2,5 vezes mais sensível do que o exame citopatológico de repetição imediata. Conclusão: O teste de DM por p16 e Ki67 se mostrou mais capaz de identificar mulheres com lesões precursoras com resultado citopatológico prévio ASC-US ou LSIL e sem aumento relevante de encaminhamentos para colposcopia em comparação à citologia de repetição imediata.(AU)

Objective: To access p16/Ki-67 double staining (DS) in cervical cells performance for detecting precursor lesions of cervical cancer, in comparison to immediate repetition of the liquid-based cervical cytology (LBCC) in women with screening cytology results of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL). Methodology: This study recruited 121 women in primary health care units in Palmas and Porto Nacional, Tocantins, and in Rio de Janeiro, Brazil, with screening cytology showing ASC-US or LSIL. Women were addressed to the Cervical Referral Services (SRC) in each state and examined with colposcopy, LBCC and DS-p16/Ki-67. Histological results were available for women in which a cervical biopsy was obtained during initial evaluation or duringa follow-up up to 12 months, discerning cases with precursor lesions (CIN2 or CIN3) or not. Results: From the 121 recruited women, 76 screened positive in at least one exam (LBCC or DS-p16/Ki-67) and had a diagnostic conclusion. From these, 42 and 34 patients had previous ASC-US and LSIL exams, respectively. Most patients (86,8%) were within the recommended age group for screening in Brazil (25 to 64 years-old). CIN2-3 were found in 8 women (10,5%). DS-p16/Ki-67 identified a greater number of women with CIN2-3, addressing 50% of the women to colposcopy, but failing to detect these lesions in 50% of cases. DS-p16/Ki-67 was2,5x more sensitive than the immediate repetition of the LBCC. Conclusion: DS-p16/Ki-67 is more efficient to identify women with precursor lesions with screening cytopalotogical ASC-US or LSIL results, and without relevant increase in referring patients to colposcopy, in comparison to immediate repetition of the LBCC.(AU)

Variability in the Epithelial Expression of Ki67 and Polarization Characteristics of Collagen in Odontogenic Cysts and Tumours

ABSTRACT Objective: To assess the proliferation of epithelium (using the Ki67 index) and the polarization pattern of collagen in selected odontogenic cysts and tumours. In addition, an exploratory analysis of the effect of inflammation on the proliferation rate was done. Material and Methods: Following immunohistochemical staining, the labelling/proliferation index of Ki67 was calculated. The thickness and corresponding polarization colour of 100 juxta-epithelial picrosirius red-stained collagen fibers were assessed using linear micrometry with an eyepiece reticule under × 1000 magnification. Inflammation was graded subjectively as mild, moderate, and severe. Results: Overall Ki-67 expression was higher in the radicular cyst, Odontogenic Keratocyst, Ameloblastoma, while suprabasal Ki-67 positivity was maximum in Odontogenic Keratocyst. The stromal collagen fibers in Ameloblastoma showed predominantly green birefringence, whereas Odontogenic Keratocyst had orange birefringence. There was no significant association of inflammation with Ki-67 expression or birefringence patterns. Conclusion: The highest Ki67 expression in the radicular cyst, followed by Odontogenic Keratocyst and Ameloblastoma. Differences in the collagen maturation pattern were noted innately in five lesions studied and were further influenced by inflammatory changes. Epithelial proliferation and concomitant expression of thickness and maturity of the stromal collagen are innate features of the lesion further influenced by inflammation in various odontogenic cysts and tumours and may, in turn, guide the clinical behavior.

Análisis de la coexpresión de HER2/GRB7 y su asociación con variables clinicopatológicas en un grupo de mujeres colombianas con diagnóstico de cáncer de mama invasivo / Analysis of HER2/GRB7 co-expression and its association with clinicopathological variables in a group of Colombian women diagnosed with invasive breast cancer

Objetivo. Analizar las diferencias en la presentación de variables clínico-patológicas, de acuerdo con la expresión proteica de GRB7, en tumores HER2 positivos en mujeres colombianas con cáncer de mama invasivo, diagnosticado entre los años 2013 y 2015 en el Instituto Nacional de Cancerología E.S.E (INC). Métodos. Se incluyeron 158 pacientes con diagnóstico confirmado de cáncer de mama ductal invasivo. Se evaluó la expresión de los receptores hormonales (receptor de estrógeno (RE) y de progesterona (RP)), HER2, Ki67 y GRB7, mediante inmunohistoquímica (IHQ), y a partir de estos, se clasificaron los tumores en subtipos intrínsecos. Los análisis estadísticos incluyeron las pruebas de Chi-cuadrado/test exacto de Fisher para las variables categóricas, y la prueba U Mann Whitney/ Kruskal Wallis para las variables cuantitativas. Se evaluó la supervivencia global (SG) y libre de enfermedad (SLR) según la coexpresión de HER2/GRB7 usando el método de Kaplan-Meier y el test de log-rank. Resultados. La expresión de GRB7 se observó exclusivamente en tumores HER2-positivos (luminal B/HER2+ y HER2-enriquecidos: p<0,001). Los casos HER2+/GRB7+ mostraron una mayor expresión de Ki67 (40% vs. 27,5%, p=0,029), pero una tendencia a presentar un menor tamaño tumoral (30 mm vs. 51 mm, p=0,097), comparado con los tumores HER2+/GRB7-. No obstante, no se observaron diferencias en la supervivencia según la coexpresión de HER2/GRB7 (SG: p=0,6; SLR: p=0,07). Conclusiones. En nuestra muestra de estudio, la expresión de GRB7 en tumores HER2+ no se asoció con características clínico-patológicas de pronóstico desfavorable.

Objective: To analyze differences in the presentation of clinicopathological variables according to GRB7 protein expression in HER2-positive tumors in Colombian patients with invasive ductal breast carcinomas diagnosed between 2013 and 2015 at the Instituto Nacional de Cancerología (Bogotá, Colombia).Methods: A total of 158 breast cancer patients were included with a confirmed diagnosis of invasive ductal carcinoma. A single pathologist evaluated the protein expression of hormone receptors (estrogen (ER) and progesterone receptor (PR)), HER2, Ki67, and GRB7 by immunohistochemistry (IHC). The chi-square and Fisher's exact tests were used to assess differences between categorical variables, as well as the Mann-Whitney/Kruskal-Wallis U test for numerical variables. Overall (OS) and disease-free (DFS) survival were evaluated according to HER2/GRB7 co-expression using the Kaplan-Meier method and log-rank test.Results:GRB7 expression was observed exclusively in HER2-positive tumors (luminal B/HER2+ and HER2-enriched: p<0.001). HER2+/GRB7+ cases showed higher Ki67 expression (40% vs. 27.5%, p=0.029) and a tendency to present a smaller tumor (30 mm vs. 51 mm, p=0.097) compared to HER2+/GRB7- tumors. However, no differences in OS or DFS were observed by HER2/GRB7 co-expression (OS: p=0.6; DFS: p=0.07).Conclusions:Our results in Colombian patients indicate that GRB7 expression in HER2-positive breast tumors is not associated with unfavorable clinicopathological features.

Use of artificial intelligence to predict response to neoadjuvant chemotherapy in breast cancer

:Breast cancer is the object of thousands of studies worldwide. Nevertheless, few tools are available to corroborate prediction of response to neoadjuvant chemotherapy. Artificial intelligence is being researched for its potential utility in several fields of knowledge, including oncology. The development of a standardized Artificial intelligence-based predictive model for patients with breast cancer may help make clinical management more personalized and effective. We aimed to apply Artificial intelligence models to predict the response to neoadjuvant chemotherapy based solely on clinical and pathological data. Methods: Medical records of 130 patients treated with neoadjuvant chemotherapy were reviewed and divided into two groups: 90 samples to train the network and 40 samples to perform prospective testingand validate the results obtained by the Artificial intelligence method. Results: Using clinicopathologic data alone, the artificial neural network was able to correctly predict pathologic complete response in 83.3% of the cases. It also correctly predicted 95.6% of locoregional recurrence, as well as correctly determined whether patients were alive or dead at a given time point in 90% of the time. To date, no published research has used clinicopathologic data to predict the response to neoadjuvant chemotherapy in patients with breast cancer, thus highlighting the importance of the present study. Conclusions: Artificial neural network may become an interesting tool for predicting response to neoadjuvant chemotherapy, locoregional recurrence, systemic disease progression, and survival in patients with breast cancer (AU)

Efficacy of neoadjuvant therapy on HER2-positive breast cancer: a clinicopathological analysis / 中华病理学杂志

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.

Association of Serine/Threonine Phosphoprotein Phosphatase 4C Expression With Prognosis of Gastric Cancer / 中国医学科学院学报

Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.

Clinicopathological and immunohistochemical analysis of maxillofacial granular cell tumor / 华西口腔医学杂志

OBJECTIVES@#To analyze the clinicopathological features of maxillofacial granular cell tumors (GCT) with the aid of immunohistochemical staining.@*METHODS@#Seven cases of maxillofacial GCT were retrospectively collated, and the microscopic morphology of maxillofacial GCT was analyzed. The expression of S-100, neuron-specific enolase (NSE), SOX-10, CD68, actin, desmin, and Ki-67 in GCT was detected by immunohistochemical staining. The cases were observed in the follow-ups after clinical treatment.@*RESULTS@#All seven GCT tumors lacked envelopes and were poorly defined. Microscopically, the sizes of the tumor cells were large and appeared with inconspicuous cell membranes, forming a syncytium-like appearance. The cytoplasm was filled with characteristic eosinophilic granules. The immunohistochemical results showed that six cases were NSE-positive, five cases were S-100-positive, seven cases were CD68-positive, five cases were SOX-10-positive, one case was actin-positive, and seven cases were desmin-negative. The Ki-67 index did not exceed 5% in all cases. In the follow-up sessions, none of the six cases presented a recurrence.@*CONCLUSIONS@#Maxillofacial GCT has a characteristic histological structure. Immunohistochemical S-100, CD68, and other indicators can assist in diagnosis, and the prognosis is good after clinical resection.

A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression / 中华医学杂志(英文版)

BACKGROUND@#In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model.@*METHODS@#Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors.@*RESULTS@#In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%.@*CONCLUSION@#Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events.@*REGISTRITATION@#ChiCTR.org.cn, ChiCTR2100046766.

The Clinical-Biological Features and Prognosis of Patients with Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical-biological features and outcomes of patients with mantle cell lymphoma (MCL).@*METHODS@#The clinical and laboratory data of 104 patients with newly diagnosed MCL who were admitted to the Department of Hematology, Fujian Medical University Union Hospital from January 2011 to December 2019 were retrospectively analyzed, and the efficacy was observed through survival analysis.@*RESULTS@#Among 104 MCL patients, 88 were male and 16 were female. The median age was 54 (25-79) years old, 93.0% (93/100) of the patients with advanced stage (III and IV stages) and 48.08% (50/104) of the patients with bone marrow infiltration. Patients with Ki-67≥50% had higher WBC counts and LDH levels. Univariate analysis showed that the patients with WBC≥15×109/L, bone marrow involvement, high LDH, high β2-MG levels, Ki-67≥50%, SOX11-, had lower OS and EFS rates (P =0.005, 0.049, 0.033, 0.025, 0.042, 0.018 and 0.001, 0.021, 0.024, 0.035, 0.014, 0.026). The OS rate and EFS rate of patients in R-CHOP and R-Hyper-CVAD treatment groups were significantly higher than those in other treatment groups (P =0.02, 0.002 and P =0.001, 0.001). Patients with autologous stem cell transplantation (ASCT) had higher OS rate and EFS rate (P =0.037, 0.013). Multivariate COX analysis showed that only WBC count, SOX11 expression and whether achieved CR after 4 courses treatment were the independent factors affecting the prognosis.@*CONCLUSION@#MCL mainly occur in elderly men. There are many factors affecting patients' survival, while WBC≥15×109/L, negative expression of SOX11 and failure to achieve CR after 4 courses of treatment are adverse factors for MCL patients.

Effect of LINC00174 on the Malignant Proliferation of Multiple Myeloma Cells and Its Related Mechanism / 中国实验血液学杂志

OBJECTIVE@#To explore the biological function of LINC00174 in multiple myeloma (MM).@*METHODS@#Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of LINC00174 and miR-150 in peripheral blood of MM patients and MM cell lines. EdU staining and flow cytometry were used to detect the effects of LINC00174 and miR-150 on the proliferation and apoptosis of MM cells. Western blot was used to detect the expressions of proliferation marker nuclear-related antigen Ki67, apoptosis-related protein cleaved caspase-3 and transcription factor forkhead box protein P1 (FOXP1). Bioinformatics and dual-luciferase reporter assay were used to verify the targeting relationship between LINC00174 and miR-150 and the targeting relationship between miR-150 and FOXP1.@*RESULTS@#The level of LINC00174 was significantly increased in peripheral blood of MM patients and MM cell lines (P <0.05). Compared with NC-siRNA group, the expression of LINC00174 was significantly reduced in LINC00174-siRNA group, the proliferation of U266 cells was reduced, the apoptosis rate was significantly increased, the level of Ki67 protein was reduced, and the level of cleaved caspase-3 protein was increased (all P <0.05). LINC00174 targeted regulation of the expression of miR-150. Compared with LINC00174-siRNA+NC inhibitor group, the expression of miR-150 in U266 cells in LINC00174-siRNA+miR-150 inhibitor group was significantly reduced, the cell proliferation was enhanced, the apoptosis rate was reduced, the level of Ki67 protein was increased, and the level of cleaved caspase-3 was decreased (all P <0.05). FOXP1 is the target gene of miR-150. Compared with NC mimic group, the expression of FOXP1 protein in miR-150 mimic group was significantly reduced, the cell proliferation was reduced, the apoptosis rate was significantly increased, Ki67 protein level was decreased, and the level of cleaved caspase-3 was increased. Compared with miR-150 mimic + vector group, the expression of FOXP1 protein in miR-150 mimic + pcDNA-FOXP1 group was significantly increased, the cell proliferation was enhanced, the apoptosis rate was reduced, the level of Ki67 protein was increased, and the level of cleaved caspase-3 was decreased (all P <0.05).@*CONCLUSION@#LINC00174 promotes the proliferation of MM cells and inhibits cell apoptosis by regulating the miR-150/ FOXP1 axis.

Treatment of paclitaxel and doxorubicin changes the immune microenvironment of breast cancer and inhibits the growth of tumor cells in mice / 细胞与分子免疫学杂志

Objective To investigate the effects of paclitaxel and doxorubicin on the immune microenvironment of breast cancer in mice. Methods The CTR-DB database, a database for analysis of gene expression profiles and drug resistance characteristics related to tumor drug response, was used to analyze the effect of chemotherapeutic drugs on the immune microenvironment of breast cancer. Mouse models with breast cancer were established by in situ injection with 4T1 cells, a triple-negative breast cancer (TNBC) cells. Then they were treated with doxorubicin and paclitaxel, respectively. The sizes of tumor were recorded and analyzed by growth curve. The number of different types of immune cells was analyzed using flow cytometry. The expressions of Ki67, S100 calcium binding protein A9 (S100A9) and matrix metalloproteinase 9 (MMP9) were detected by immunohistochemistry. The cell cycles of 4T1 cells in paclitaxel group and doxorubicin group were analyzed by flow cytometry. Results The results of CTR_Microarray_75 analysis showed that the immune scores, and the number of cytotoxic lymphocytes, B lineages, CD8+ T cells, dendritic cells (DCs), monocytic lineages and natural killer (NK) cells in chemotherapy-sensitive breast cancer were higher than those in chemotherapy-insensitive breast cancer. Through growth curve analysis in mice with breast cancer, we found that both paclitaxel and doxorubicin could inhibit the increase of the tumor sizes, and the paclitaxel showed a higher inhibitory effect. The results of cytometry displayed that both paclitaxel and doxorubicin could restrain the expression of Ki67 and increase the number of breast cancer cells in G2/M phase, and in the paclitaxel group, the expression of Ki67 was lower and the number of breast cancer cells in G2/M phase was larger. Paclitaxel and doxorubicin enhanced the infiltration of CD45+ immune cells but decreased the infiltration of neutrophils. Additionally, paclitaxel promoted the infiltration of CD3+CD4+ T helper cells, CD3+CD8+ cytotoxic T cells and CD45+CD19+B cells, while doxorubicin increased the infiltration of CD4+CD25+ regulatory T cells (Tregs). The results of immunohistochemistry displayed that the paclitaxel significantly inhibited the expression of S100A9, while the doxorubicin significantly restrained the expression of MMP9. Conclusion Paclitaxel and doxorubicin can effectively inhibit the growth of breast cancer cells and change immune microenvironment of TNBC by regulating the different patterns of cell infiltration and the expression of different extracellular matrix components.

FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.@*METHODS@#The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.@*RESULTS@#GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).@*CONCLUSION@#FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.

HSDL2 overexpression promotes rectal cancer progression by regulating cancer cell cycle and promoting cell proliferation / 南方医科大学学报

OBJECTIVE@#To analyze the expression of hydroxysteroid dehydrogenase like 2 (HSDL2) in rectal cancer tissues and the effect of changes in HSDL2 expression level on proliferation of rectal cancer cells.@*METHODS@#Clinical data and tissue samples of 90 patients with rectal cancer admitted to our hospital from January 2020 to June 2022 were collected from the prospective clinical database and biological specimen database. The expression level of HSDL2 in rectal cancer and adjacent tissues was detected by immunohistochemistry, and based on the median level of HSDL2 expression, the patients were divided into high expression group (n=45) and low expression group (n=45) for analysis the correlation between HSDL2 expression level and the clinicopathological parameters. GO and KEGG enrichment analyses were performed to explore the role of HSDL2 in rectal cancer progression. The effects of changes in HSDL2 expression levels on rectal cancer cell proliferation, cell cycle and protein expressions were investigated in SW480 cells with lentivirus-mediated HSDL2 silencing or HSDL2 overexpression using CCK-8 assay, flow cytometry and Western blotting.@*RESULTS@#The expressions of HSDL2 and Ki67 were significantly higher in rectal cancer tissues than in the adjacent tissues (P < 0.05). Spearman correlation analysis showed that the expression of HSDL2 protein was positively correlated with Ki67, CEA and CA19-9 expressions (P < 0.01). The rectal cancer patients with high HSDL2 expressions had significantly higher likelihood of having CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T3-4 stage, and N2-3 stage than those with a low HSDL2 expression (P < 0.05). GO and KEGG analysis showed that HSDL2 was mainly enriched in DNA replication and cell cycle. In SW480 cells, HSDL2 overexpression significantly promoted cell proliferation, increased cell percentage in S phase, and enhanced the expression levels of CDK6 and cyclinD1 (P < 0.05), and HSDL2 silencing produced the opposite effects (P < 0.05).@*CONCLUSION@#The high expression of HSDL2 in rectal cancer participates in malignant progression of the tumor by promoting the proliferation and cell cycle progress of the cancer cells.

Neoadjuvant chemotherapy in the treatment of locally advanced olfactory neuroblastoma in 25 cases / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [M (Q1, Q3)]. The change of Ki-67 before and after NACT was statistically significant (Z=-24.24, P<0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P<0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.

Clinicopathological features and prognosis of breast cancer with human epidermal growth factor receptor 2 low expression / 北京大学学报(医学版)

OBJECTIVE@#There is an increasing interest in human epidermal growth factor receptor 2 (HER2) low expression breast cancer with the result of novel anti-HER2 antibody-drug conjugates for breast cancer. HER2 low expression breast cancer is expected to become a new type of breast cancer. This study analyzed and compared the clinicopathological features and survival data of breast cancer with HER2 low expression group [immunohistochemistry (IHC) 1+ or IHC 2+, and fluorescence in situ hybridization (FISH) negative] and HER2 zero expression group (IHC 0), in order to explore the difference in clinical biology of HER2 low expression breast cancers.@*METHODS@#Among 1 250 female patients with primary non-metastatic breast cancer admitted to the Breast Disease Center of Peking University First Hospital from January 2014 to December 2017, 969 cases were HER2 negative (IHC 0, 1+, 2+, and FISH was not amplified). The clinicopathologic features and prognosis of the patients with HER2 low expression (IHC 1+ or 2+, and unamplified by FISH) and HER2 zero expression (IHC 0) were analyzed. Disease free survival (DFS) and overall survival (OS) were evaluated, survival rates were calculated by Kaplan-Meier curve, and survival differences were compared by Log-rank test. Cox regression analysis of univariate and multivariate prognostic factors. Bilateral test was used, and P < 0.05 was considered statistically significant.@*RESULTS@#In the 969 patients with HER2 negative breast cancer, 606 had HER2 low expression (62.54%) and 363 had HER2 zero expression (37.46%). Compared with breast cancer with HER2 zero expression, those with HER2 low expression had higher N stage (P=0.001) and TNM stage (P=0.044), the proportion of non-specific histological types was higher (82.7% vs. 79.1%, P=0.009), the histological grade was higher (P=0.048), and the positive rate of hormone receptor was higher (83.2% vs. 75.2%, P=0.003). The percentage of Ki-67 value index >30% was lower (30.4% vs. 36.6%, P=0.044). There was no significant difference in DFS and OS between the two groups (P>0.05). In the 969 cases, 777 were hormone receptor positive and 192 were hormone receptor negative (triple negative cancer). Among the 777 cases with hormone receptor positive, 504 (64.9%) were HER2 low expression, and 273 (35.1%) were HER2 zero expression. Compared with breast cancer with HER2 zero expression group, the HER2 low expression group had a younger age (P=0.016), a higher proportion of premenopausal patients (P=0.029), more lymph node involvement (P=0.002), and a higher total TNM stage (P=0.031), and less frequent histological types of lobular and mucinous carcinoma (3.6% vs. 7.3%, 4.8% vs. 10.6%, P=0.001). There was no difference in DFS and OS between HER2 low expression and zero expression (P>0.05). Among 192 patients with hormone receptor negative, there were 102 cases (53.1%) with HER2 low expression and 90 cases (46.9%) with HER2 zero expression. Compared with the HER2 zero expression groups, HER2 low expression group was older (P=0.001), the proportion of premenopausal patients was low (P=0.029), the histological grade was lower (P < 0.001), the Ki-67 value index was lower (P < 0.001), and androgen receptor positive rate was higher (58.8% vs. 34.4%, P < 0.001). DFS was better than HER2 zero expression group (P=0.038), but there was no difference in OS between the two groups (P>0.05).@*CONCLUSION@#HER2 low expression breast cancer accounts for about half of all breast cancers, and the incidence is much higher than that of HER2 positive breast cancer. Its clinicopathologic features are heterogeneous, and the status of hormone receptor expression has an impact on the clinical biology of this group.

Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients / 中华胃肠外科杂志

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Analysis of clinicopathological features of 18 cases of hepatic angiosarcoma / 中华肝脏病杂志

Objective: To investigate the clinicopathological features, treatment, and prognosis of hepatic angiosarcoma. Methods: Clinicopathological data and prognostic conditions of 18 cases with hepatic angiosarcoma were collected retrospectively. The recurrence-free survival rate and overall survival rate were calculated by the Kaplan-Meier method. A Cox regression analysis was used to explore the survival-related risk factors. Results: There were 12 male and 6 female patients, with an average age of 57 (37 ~ 70) years. The tumor's average diameter was 8.40 (2.00 ~ 18.00) cm. Seven cases had multiple tumors, while two cases had large vessel tumor thrombuses. Microscopically, the tumor tissues were irregularly anastomosed, with vascular lacunar or solid bundle-like weaving, and the tissue morphology mimicked capillary hemangioma, cavernous hemangioma, or angioepithelioma, while tumor cells were spindle-shaped or epithelioid, lined with hobnails in the lumen, or formed papillary structures in the lumen. The proportion of highly, moderately, and poorly differentiated tumors was 4:8:6, with six cases having clear tumor boundaries, eight having microvascular tumor thrombi, and sixteen having blood lake formation. Different levels of expression of CD31, CD34, erythroblast transformation-specific related genes, and Fli-1 markers were demonstrated in all of the cases. Four cases had a P53 mutation, and six cases had Ki-67 > 10%. During the follow-up period of 0.23-114.20 months, the five-year recurrence-free survival rate and overall survival rate were 16.7% and 37.2%, respectively. Cox regression multivariate analysis showed that preoperative symptoms and multiple tumors were significant risk factors for recurrence-free survival, while preoperative symptoms and Ki-67 > 10% were significant risk factors for overall survival. Conclusion: Hepatic angiosarcoma is a rare hepatic mesenchymal tumor with high malignancy and a poor prognosis. Pathological morphology and immunohistochemical marker combinations are needed for a definite diagnosis. However, the complexity of angiosarcomas' histological and cytological conformations and the overlap of pathological features with benign vascular tumors, sarcomas, and carcinomas pose difficulties in the differential diagnosis. Thus, the only effective ways to prolong survival are early detection and radical surgical resection.

Clinicopathological analysis of pseudostratified ependymal tubules in ovarian mature teratoma / 中华病理学杂志

Objective: To investigate the morphology and immunohistochemical (IHC) expression of pseudostratified ependymal tubules in ovarian mature teratoma (MT). Methods: Five cases of ovarian MT with pseudostratified ependymal tubules were collected from Shenzhen Hospital(Futian) of Guangzhou University of Chinese Medicine and the Eighth Affiliated Hospital of Sun Yat-sen University from March 2019 to March 2022. In addition, 15 cases of ovarian MT with monolayer ependymal epithelium from Shenzhen Hospital (Futian) of Guangzhou University of Chinese medicine and seven cases of immature teratoma (IMT) from Hainan Provincial People's Hospital from March 2019 to March 2022 were collected as control. The morphologic characteristics and immunophenotypes of pseudostratified ependymal tubules, monolayer ependymal epithelium, and primitive neural epithelial tubules were observed and compared by H&E stain and IHC expression pattern of genes related to the differentiation status of neuroepithelium, namely SALL4, Glypican3, nestin, SOX2, Foxj1, and Ki-67. Results: Mean age of the five patients of ovarian MT with pseudostratified ependymal tubules was 26 years (range from 19 to 31 years). Two tumors were located in the left ovary and three in the right. All five cases were excised, and clinical follow-up was available (mean follow-up 1.5 years; range 0.5 to 3 years). No recurrence was noted in any cases. The pseudostratified ependymal tubules of ovarian MT, which were lined with columnar or oval epithelia up to 4-6 layers, were morphologically similar to the primitive neuroepithelial tubules of IMT and different from monolayer ependymal epithelium of ovarian MT. By immunohistochemistry, SALL4 and Glypican3 were negative, Foxj1 was positive and Ki-67 index was lower in the pseudostratified ependymal tubules and the monolayer ependymal epithelium of ovarian MT. However, the primitive neuroepithelial tubules of IMT showed variably expression of SALL4 and Glypican3, were negative for Foxj1 and high Ki-67 index. All the above three groups expressed nestin and SOX2. Conclusions: The pseudostratified ependymal tubules of ovarian MT, which have morphological similarities to the primitive neuroepithelial tubules of IMT, are similar to the monolayer ependymal epithelia of the MT in immunophenotype. IHC assessment of Foxj1 and Ki-67 is helpful to differentiate the pseudostratified ependymal tubules of ovarian MT from the primitive neuroepithelial tubules of IMT.