Diagnosis of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology / 中华神经科杂志

Endometrial carcinoma is one of common malignant tumors in female reproductive system, but it is extremely rare in leptomeningeal metastasis. The clinical manifestations and signs of meningeal carcinomatosis are complex and not specific. It is difficult to get a precise diagnosis early, and it has high rate of misdiagnosis and missed diagnosis. Accurate diagnosis and treatment of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology are reported. The patient is an elderly female with a history of endometrial cancer. The main manifestations were fever, headache and dizziness; cerebrospinal fluid cytology showed tumor cells; AKT1 gene and TP53 gene were detected in endometrial carcinoma tissue, plasma and cerebrospinal fluid by next-generation sequencing. After treatment with intrathecal chemotherapy, immunotherapy combined with anti angiogenesis, the patient′s condition still progressed gradually and died finally. The purpose of this case report is to raise clinical awareness of recognition and treatment in early meningeal metastasis of endometrial carcinoma.

Differential Expression of Androgen Receptor in Type I and Type II Endometrial Carcinomas: A Clinicopathological Analysis and Correlation with Outcome.

OBJECTIVES: Endometrial carcinomas (EC) are the most common gynecological malignancies and are conventionally divided into type I and type II due to diagnostic and prognostic considerations. Female hormone expression in EC is extensively studied; however, data about androgen receptor (AR) expression in EC are sparse. We aimed to study AR expression in different types of EC at our institute and whether it had an impact on patient outcomes. METHODS: A retrospective analysis of EC cases diagnosed and treated from 2010-2019. AR immunohistochemical expression was tested in 52 EC cases (type I = 40; type II = 12). Histological typing was verified according to conventional diagnostic criteria. Only primary EC were included without neoadjuvant therapy. Histologic score was calculated as: stain intensity (graded 0-3) × positive cells percentage (graded 0-4). Level of expression was scored from 0 to 12. RESULTS: The mean age of the selected patients was 60.3 years (range = 31-88 ± 12.6). Recurrence was detected in 11 (21.2%) patients. The outcome was 40 patients were alive without disease, eight alive with disease, three dead of disease, and one dead of other causes. About 62.5% of type I-EC and 25.0% of type II-EC were AR positive. AR expression was analyzed against different clinicopathological parameters including: type (p = 0.005), histotype (p = 0.044); grade (p = 0.035); age group (p = 0.207); menopause (p = 0.086); estrogen receptor (ER) expression (p = 0.284); atypical complex hyperplasia (p = 0.594); tumor stage (p = 0.994); tumor recurrence (p = 0.530); node status (p = 0.110); and outcome (p = 0.202). CONCLUSION: AR expression was higher in type I EC, endometrial endometrioid carcinoma histotype, and with a lower grade. AR expression was not significantly correlated with age, stage, ER, atypical hyperplasia, recurrence, node status, or outcome. Results agree with recent literature that AR expression is associated with better-differentiated EC and may be a potential hormonal therapeutic tool.

Does complete-staging lymphadenectomy improve survival outcomes in stage I endometrioid epithelial ovarian carcinoma? A multi-institutional retrospective study with propensity score-weighted analysis.

BACKGROUND: We investigated the prognostic impact of complete-staging lymphadenectomy on patients with clinically apparent Stage I endometrioid epithelial ovarian carcinoma. METHODS: We conducted a regional multi-institutional retrospective study between 1986 and 2018. Amongst 4897 patients with malignant ovarian tumours diagnosed under central pathological review, 259 women with Stage I endometrioid epithelial ovarian carcinoma were eligible. We evaluated differences in survival of patients with both pelvic and para-aortic lymphadenectomy (Group A) and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation (Group B). To analyse the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. RESULTS: In total, 145 patients (56.0%) received both pelvic and para-aortic lymphadenectomy. With propensity score-based adjustment, estimated survival was better in Group A compared with that in Group B but not significant. Pelvic and para-aortic lymphadenectomy also led to no significant improvement of overall survival in most of the subgroups. However, point estimations of the hazard ratio for lymphadenectomy in patients with an age of 45 or younger (hazard ratio, 0.304; 95% confidence interval, 0.094-0.982), a Grade 1-2 (hazard ratio, 0.441; 95% confidence interval, 0.204-0.954) and T1c2-3 tumour (hazard ratio, 0.449; 95% confidence interval, 0.164-1.231) were better compared with those with the opposite characteristics. CONCLUSIONS: Complete-staging lymphadenectomy was not a significant prognostic factor in patients with Stage I endometrioid epithelial ovarian carcinoma, where we still need to explore appropriate candidate for the procedure.

Primary broad ligament adenocarcinoma.

Primary broad ligament carcinoma is a very rare occurrence with 28 reported cases worldwide, to date. The epidemiology, treatment strategy and prognosis are still uncertain because of the scarcity of cases. Currently, all broad ligament carcinomas are managed similar to epithelial ovarian cancer. We report the case of a 43-year-old female with a prolonged complaint of abdominal pain and intermittent urinary retention, requiring frequent catheterization. She was diagnosed with obstructive right hydroureteronephrosis. The abdominal Contrast Enhanced Computed Tomography (CECT) revealed a well-defined heterogeneous lesion of 2.1х3х3.2cm size in the right lateral and posterior wall of the cervix. An ultrasound (USG)-guided Fine Needle Aspiration Cytology (FNAC) of the mass was done and it was suspected to be malignant. The patient underwent total abdominal hysterectomy, right salpingo-oophorectomy, pelvic lymph-nodal sampling, and peritoneal washing. Histological examination depicted an endometrioid adenocarcinoma of the broad ligament. She received adjuvant chemotherapy, followed by hormonal therapy. It has been five years since her surgery, and she is now alive and disease free.

Response to Multi-Line Chemotherapy in Non-Serous Epithelial Ovarian Cancer.

OBJECTIVES: To describe the response rate to chemotherapy, rates of recurrence, and overall survival in patients with non-serous epithelial ovarian cancers. METHODS: This retrospective cohort study used the Manitoba Cancer Registry to identify all women with non-serous epithelial ovarian, fallopian, or peritoneal cancer treated between 1995 and 2010. Chart review entailed extracting information regarding therapy and outcomes. All patients with recurrence were identified and response to chemotherapy was assessed. RESULTS: We identified 392 patients with non-serous ovarian cancers, 192 of whom received chemotherapy in the first-line setting. Optimal debulking resulted in improvements in rates of recurrence and overall survival (P < 0.001). Histology did not have an effect on recurrence or overall survival. Forty-eight patients (25%) had a recurrence and received second-line therapy, and 21 (11%) received third-line therapy. Response rates were similar regardless of histology. In the second-line setting, 40.9%-83.3% of patients (other > mucinous > clear cell > endometrioid) and in the third-line setting, 33.3%-75.0% of patients (other > mucinous > clear cell > endometrioid) received >6 lines of chemotherapy. Twenty-three percent of patients experienced a recurrence within 2 years of first-line therapy. Two-year survival was 79.4% after first-line treatment, 27.6% after second-line treatment, and 19.5% after third-line treatment. CONCLUSION: Patients with clear cell ovarian cancer had chemotherapy continuation rates similar to those of previously reported studies. This is one of the first studies reporting response rates for mucinous and endometrioid subtypes. Recurrent disease responds to treatment with second- and third-line therapy, emphasizing the importance of offering patients subsequent lines of chemotherapy for disease management. Further studies are needed to determine the optimal regimen.

[Characteristic and clinical significance of microRNA expression between 144 Uygur and Han women with endometrial carcinoma].

OBJECTIVE: To compare the expression patterns of microRNA (miRNA) between 144 Uygur and Han women with endometrial carcinoma and to investigate their clinical significance. METHODS: Taqman miRNA low-density array was used to compare miRNA profiles between Uygur and Han women with non-endometrioid endometrial carcinoma (NEEC). Five miRNAs were further analyzed in the 144 endometrial cancers including 62 Uygur and 82 Han samples via real-time PCR to determine their expression patterns. RESULTS: MiRNA expression profiles revealed that many miRNAs overexpressed or downregula-ted in one ethnic group, but did not express or changed slightly in the other ethnic group. Further detection in the 144 endometrial cancers showed that miR-141, miR-200a, and miR-205 overexpressed in both ethnic groups. In Uygur endometrioid endometrial carcinoma (EEC), tumors with miR-141/200a overexpression tended to be more aggressive in behavior, whereas in the Han group, EEC with miR-200a overexpression was relative mild. However, the NEEC with miR-200a overexpression also had aggressive clinicopathologic features in the Han women. MiR-145 and miR-143 expressed differentially between Uygur and Han groups, they overexpressed in the former and decreased in the latter (P<0.05). In the Uygur women miR-145/143 increased significantly in NEEC and there was a trend that NEEC exhibiting favorable clinicopathologic factors had higher miR-145 expression, and was statistically significant in tumors with myometrial invasion less than 1/2 thickness (P=0.042). By contrary, miR-145/143 decreased in Han group and EEC with worse clinicopathologic variables had lower expression although without statistical significance. NEEC in Han group had no such tendency. CONCLUSION: Uygur and Han women might have different miRNA expression profiles. MiR-141/200a/205 overexpressed in endometrial carcinomas and miR-141/200a might behave differently between these two ethnic groups as well as in EEC and in NEEC. Although miR-145/143 showed inverse expression patterns between Uygur and Han women with endometrial cancer, they all exerted tumor suppression effect on endometrial cancer.

Development of localized cul-de-sac endometrioid carcinoma associated with deep infiltrating endometriosis during remission of early endometrial cancer.

•A cul-de-sac endometrioid carcinoma adjacent to extraovarian endometriosis was identified during remission of endometrial cancer.•The origin of the cul-de-sac tumor was malignant transformation of deep infiltrating endometriosis.•Endometriosis-related cancer was identified in a woman with endometrial cancer during remission.•Hyperestrogenism due to infertility treatment may contribute to malignant transformation of deep infiltrating endometriosis.

Primary broad ligament adenocarcinoma

Primary broad ligament carcinoma is a very rare occurrence with 28 reported cases worldwide, to date. The epidemiology, treatment strategy and prognosis are still uncertain because of the scarcity of cases. Currently, all broad ligament carcinomas are managed similar to epithelial ovarian cancer. We report the case of a 43-year-old female with a prolonged complaint of abdominal pain and intermittent urinary retention, requiring frequent catheterization. She was diagnosed with obstructive right hydroureteronephrosis. The abdominal Contrast Enhanced Computed Tomography (CECT) revealed a well-defined heterogeneous lesion of 2.1х3х3.2cm size in the right lateral and posterior wall of the cervix. An ultrasound (USG)-guided Fine Needle Aspiration Cytology (FNAC) of the mass was done and it was suspected to be malignant. The patient underwent total abdominal hysterectomy, right salpingo-oophorectomy, pelvic lymph-nodal sampling, and peritoneal washing. Histological examination depicted an endometrioid adenocarcinoma of the broad ligament. She received adjuvant chemotherapy, followed by hormonal therapy. It has been five years since her surgery, and she is now alive and disease free.

Characteristic and clinical significance of microRNA expression between 144 Uygur and Han women with endometrial carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To compare the expression patterns of microRNA (miRNA) between 144 Uygur and Han women with endometrial carcinoma and to investigate their clinical significance.@*METHODS@#Taqman miRNA low-density array was used to compare miRNA profiles between Uygur and Han women with non-endometrioid endometrial carcinoma (NEEC). Five miRNAs were further analyzed in the 144 endometrial cancers including 62 Uygur and 82 Han samples via real-time PCR to determine their expression patterns.@*RESULTS@#MiRNA expression profiles revealed that many miRNAs overexpressed or downregula-ted in one ethnic group, but did not express or changed slightly in the other ethnic group. Further detection in the 144 endometrial cancers showed that miR-141, miR-200a, and miR-205 overexpressed in both ethnic groups. In Uygur endometrioid endometrial carcinoma (EEC), tumors with miR-141/200a overexpression tended to be more aggressive in behavior, whereas in the Han group, EEC with miR-200a overexpression was relative mild. However, the NEEC with miR-200a overexpression also had aggressive clinicopathologic features in the Han women. MiR-145 and miR-143 expressed differentially between Uygur and Han groups, they overexpressed in the former and decreased in the latter (P<0.05). In the Uygur women miR-145/143 increased significantly in NEEC and there was a trend that NEEC exhibiting favorable clinicopathologic factors had higher miR-145 expression, and was statistically significant in tumors with myometrial invasion less than 1/2 thickness (P=0.042). By contrary, miR-145/143 decreased in Han group and EEC with worse clinicopathologic variables had lower expression although without statistical significance. NEEC in Han group had no such tendency.@*CONCLUSION@#Uygur and Han women might have different miRNA expression profiles. MiR-141/200a/205 overexpressed in endometrial carcinomas and miR-141/200a might behave differently between these two ethnic groups as well as in EEC and in NEEC. Although miR-145/143 showed inverse expression patterns between Uygur and Han women with endometrial cancer, they all exerted tumor suppression effect on endometrial cancer.

[Clinical application of TCGA molecular classification in endometrial endometrioid carcinoma].

Objective: To explore molecular characteristics of endometrial endometrioid cancer according to The Cancer Genome Atlas (TCGA) based molecular classification of endometrial carcinomas and to confirm simple and clinically applicable surrogate methodologies in pathological practice. Methods: Two hundred and twenty-eight cases of endometrial endometroid adenocarcinomas (EnACs) collected from August 2001 to August 2017 from Peking University Health Science Center, Peking University Third Hospital were molecularly categorized by using Sanger sequencing for the exonuclease domain mutations (EDM) of POLE, and by immunohistochemistry for p53 and mismatch repair (MMR) proteins. The cohort was classified into polymerase-E exonuclease domain mutation (POLE EDM), mismatch repair deficiency (MMR-D), p53 abnormal (p53-abn) and p53 wild type (p53-wt) groups. The correlation between molecular subgroups and the clinical-pathological features including prognosis were analyzed. Results: The cohort was distributed as follows: 11(4.8%) POLE EDM, 47(20.6%) MMR-D, 9(4.0%) p53-abn and 161(70.6%) p53-wt. p53-wt subgroup patients demonstrated significantly higher lymph node metastasis (P=0.011) and more advanced stage (P=0.036) than those of somatic hypermutation group cases (POLE EDM and MMR-D). In the FIGO grade 2-3 EnACs cohort, TCGA molecular subtyping was significantly correlated with progression-free survival and overall survival (P=0.043). POLE EDM subgroup had the best survival, while p53-abn subgroup had the worst. Conclusions: Identification of POLE EDM and MMR-D subgroups provides independent and highly valuable prognostic information beyond established histological classification. Based on immunohistochemistry of MMR, p53 and POLE mutational analysis, this pragmatic molecular classification scheme can be served as a reliable surrogate for TCGA molecular classification, which has potential to be used routinely in Chinese pathological practice.

Padrão histopatológico e incidência de carcinomatose peritoneal ao diagnóstico em mulheres com câncer de ovário / Histopathological pattern and incidence of peritoneal carcinomatosis at diagnosis in women with ovarian cancer

Objetivo: Descrever o padrão histopatológico e identificar a incidência de carcinomatose peritoneal no momento do diagnóstico de mulheres diagnosticadas com neoplasia de ovário. Métodos: Trata-se de um estudo transversal e descritivo, baseado na análise secundária de dados correspondentes aos prontuários de mulheres adultas com diagnóstico de neoplasia de ovário de um serviço de referência em oncologia clínica. Foram analisados 40 prontuários entre janeiro de 2007 e janeiro de 2017. Resultados: Ao estadiamento segundo o sistema da International Federation of Gynecology and Obstetrics, três mulheres (7,5%) apresentavam estadiamento clínico (EC) II, três (77,5%) estágio ECIII com carcinomatose peritoneal/invasão da pelve e seis (15%) estágio ECIV com metástases à distância, especialmente para pulmão e fígado. Em relação ao padrão histopatológico, 20 mulheres apresentaram adenocarcinoma seroso papilífero de alto grau (50%), 4 (10%) adenocarcinoma seroso papilífero de baixo grau, 3 (7,5%) adenocarcinoma endometrioide, 3 (7,5%) tumor de teca/granulosa, 3 (7,5%) carcinoma de células claras, 3 (7,5%) tumores não classificados, 2 (5%) disgerminoma e 2 (5%) com cistoadenocarcinoma mucinosos. Conclusão: É nítida a necessidade de mais estudos envolvendo essa patologia, de modo a favorecer o diagnóstico e a intervenção em estágios mais precoces e reduzir desfechos desfavoráveis. (AU)

Objective: To describe the histopathological pattern, and to identify the incidence of peritoneal carcinomatosis at the time of the diagnosis of women diagnosed with ovarian neoplasm. Methods: This is a cross-sectional and descriptive study, based on the secondary analysis of data corresponding to the medical records of adult women diagnosed with ovarian neoplasm in a reference service of clinical oncology. A total of 40 medical records were analyzed between January 2007 and January 2017. Results: At the staging (FIGO system) of the International Federation of Gynecology and Obstetrics, three women (7.5%) had clinical staging (EC) II staging, 31 (77.5%) were in the ECIII stage, with peritoneal carcinomatosis/pelvic invasion, six (15%) were in the ECIV stage, with metastases at a distance, especially to lung and liver. Regarding the histopathological pattern, twenty women had high-grade papillary serous adenocarcinoma (50%), 4 (10%) with low-grade papillary serous adenocarcinoma, 3 (7.5%) with endometrioid adenocarcinoma, 3 (7.5%) with granulosa-theca tumor, 3 (7.5%) with clear cell carcinoma, 3 (7.5%) with unclassified tumors, 2 (5%) with dysgerminoma, two (5%) with mucinous cystadenocarcinoma. Conclusions: There is a clear need for further studies involving this pathology, in order to favor diagnosis and intervention at earlier stages and to reduce unfavorable outcomes. (AU)

Magnetic resonance imaging findings for discriminating clear cell carcinoma and endometrioid carcinoma of the ovary.

BACKGROUND: Common cancerous histological types associated with endometriosis are clear cell carcinoma (CCC) and endometrioid carcinoma (EC). CCC is regarded as an aggressive, chemoresistant histological subtype. Magnetic resonance imaging (MRI) offers some potential advantages to diagnose ovarian tumors compared with ultrasonography or computed tomography. This study aimed to identify MRI features that can be used to differentiate between CCC and EC. METHODS: We searched medical records of patients with ovarian cancers who underwent surgical treatment at Nara Medical University Hospital between January 2008 and September 2018; we identified 98 patients with CCC or EC who had undergone preoperative MRI. Contrasted MRI scans were performed less than 2 months before surgery. Patients were excluded from the study if they had no pathology, other pathological subtype of epithelial ovarian cancer, and/or salvage treatment for recurrence and metastatic ovarian cancer at the time of study initiation. Clinically relevant variables that were statistically significant by univariate analysis were selected for subsequent multivariate regression analysis to identify independent factors to distinguish CCC from EC. RESULTS: MRI of CCC and EC showed a large cystic heterogeneous mixed mass with mural nodules protruding into the cystic space. Univariate logistic regression analysis revealed that the growth pattern (broad-based nodular structures [multifocal/concentric sign] or polypoid structures [focal/eccentric sign]), surface irregularity (a smooth/regular surface or a rough/irregular/lobulated surface), "Width" of mural nodule, "Height-to-Width" ratio (HWR), and presence of preoperative ascites were factors that significantly differed between CCC and EC. In the multivariate logistic regression analysis, the growth pattern of the mural nodule (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.013-0.273, p = 0.0004) and the HWR (OR = 3.71, 95% CI: 1.128-13.438, p = 0.036) were independent predictors to distinguish CCC from EC. CONCLUSIONS: In conclusion, MRI data showed that the growth pattern of mural nodules and the HWR were independent factors that could allow differentiation between CCC and EC. This finding may be helpful to predict patient prognosis before operation.

Expression of cluster proteins in endometrial carcinoma and its relationship with ER and PR / 中国基层医药

Objective To investigate the expression of cluster proteins in endometrial cancer tissues and its correlation with estrogen receptor ( ER) and progesterone receptor ( PR).Methods We selected 120 cases of endometrial cancer tissue specimens and 120 cases of normal endometrial tissue specimens from January 2013 to December 2017 in the Maternal and Child Health Hospital of Huzhou.The expression of cluster proteins ,ER and PR in tissues were determined by immunohistochemistry.Results The positive rate of cluster proteins in the endometrial carcinoma tissues(89.2%) was higher than that in the normal endometrial tissues (13.3%) ( χ2 ＝145.067,P＜0.05).The positive expression rates of ER and PR in the endometrial carcinoma tissues (60.0%,56.7%) were lower than those in the normal endometrial tissues (100.0%,100.0%) (χ2 ＝93.490,96.698,all P＜0.05).The cluster proteins was negatively correlated with ER and PR in the endometrial carcinoma tissues ( r＝－0.472,－0.513,all P＜0.05).The expression of cluster protein and ER in the endometrial carcinoma were associated with FIGO stage , depth of myometrial invasion and lymph node metastasis of endometrial carcinoma (83.1% vs.93.0%,82.6% vs. 98.0%,97.6% vs.84.6%;81.7% vs.29.2%,91.3% vs.17.6%,19.5% vs.82.1%) ( χ2 ＝6.628,7.228, 4.779;33.062,66.292,43.984,all P＜0.05),and were not associated with age ,degree of differentiation and tumor diameter (all P＞0.05).The positive expression of PR in the endometrial carcinoma was correlated with the FIGO stage and depth of myometrial invasion of the endometrial carcinoma (78.9% vs.24.5%,84.1% vs.20.0%,χ2 ＝34.919,48.577,all P＜0.05),and were not associated with age ,degree of differentiation,tumor diameter and lymph node metastasis (all P＞0.05).Conclusion The development of endometrial cancer is related to the overexpression of cluster proteins,and the expression of cluster proteins may be regulated by estrogen and progesterone .

Clinical application of TCGA molecular classification in endometrial endometrioid carcinoma / 中华病理学杂志

Objective@#To explore molecular characteristics of endometrial endometrioid cancer according to The Cancer Genome Atlas (TCGA) based molecular classification of endometrial carcinomas and to confirm simple and clinically applicable surrogate methodologies in pathological practice.@*Methods@#Two hundred and twenty-eight cases of endometrial endometroid adenocarcinomas (EnACs) collected from August 2001 to August 2017 from Peking University Health Science Center, Peking University Third Hospital were molecularly categorized by using Sanger sequencing for the exonuclease domain mutations (EDM) of POLE, and by immunohistochemistry for p53 and mismatch repair (MMR) proteins. The cohort was classified into polymerase-E exonuclease domain mutation (POLE EDM), mismatch repair deficiency (MMR-D), p53 abnormal (p53-abn) and p53 wild type (p53-wt) groups. The correlation between molecular subgroups and the clinical-pathological features including prognosis were analyzed.@*Results@#The cohort was distributed as follows: 11(4.8%) POLE EDM, 47(20.6%) MMR-D, 9(4.0%) p53-abn and 161(70.6%) p53-wt. p53-wt subgroup patients demonstrated significantly higher lymph node metastasis (P=0.011) and more advanced stage (P=0.036) than those of somatic hypermutation group cases (POLE EDM and MMR-D). In the FIGO grade 2-3 EnACs cohort, TCGA molecular subtyping was significantly correlated with progression-free survival and overall survival (P=0.043). POLE EDM subgroup had the best survival, while p53-abn subgroup had the worst.@*Conclusions@#Identification of POLE EDM and MMR-D subgroups provides independent and highly valuable prognostic information beyond established histological classification. Based on immunohistochemistry of MMR, p53 and POLE mutational analysis, this pragmatic molecular classification scheme can be served as a reliable surrogate for TCGA molecular classification, which has potential to be used routinely in Chinese pathological practice.

Expression of cluster proteins in endometrial carcinoma and its relationship with ER and PR / 中国基层医药

Objective@#To investigate the expression of cluster proteins in endometrial cancer tissues and its correlation with estrogen receptor (ER) and progesterone receptor (PR).@*Methods@#We selected 120 cases of endometrial cancer tissue specimens and 120 cases of normal endometrial tissue specimens from January 2013 to December 2017 in the Maternal and Child Health Hospital of Huzhou.The expression of cluster proteins, ER and PR in tissues were determined by immunohistochemistry.@*Results@#The positive rate of cluster proteins in the endometrial carcinoma tissues(89.2%) was higher than that in the normal endometrial tissues(13.3%) (χ2=145.067, P<0.05). The positive expression rates of ER and PR in the endometrial carcinoma tissues(60.0%, 56.7%) were lower than those in the normal endometrial tissues(100.0%, 100.0%) (χ2=93.490, 96.698, all P<0.05). The cluster proteins was negatively correlated with ER and PR in the endometrial carcinoma tissues (r=-0.472, -0.513, all P<0.05). The expression of cluster protein and ER in the endometrial carcinoma were associated with FIGO stage, depth of myometrial invasion and lymph node metastasis of endometrial carcinoma(83.1% vs.93.0%, 82.6% vs.98.0%, 97.6% vs.84.6%; 81.7% vs.29.2%, 91.3% vs.17.6%, 19.5% vs.82.1%) (χ2=6.628, 7.228, 4.779; 33.062, 66.292, 43.984, all P<0.05), and were not associated with age, degree of differentiation and tumor diameter (all P>0.05). The positive expression of PR in the endometrial carcinoma was correlated with the FIGO stage and depth of myometrial invasion of the endometrial carcinoma(78.9% vs.24.5%, 84.1% vs.20.0%, χ2=34.919, 48.577, all P<0.05), and were not associated with age, degree of differentiation, tumor diameter and lymph node metastasis (all P>0.05).@*Conclusion@#The development of endometrial cancer is related to the overexpression of cluster proteins, and the expression of cluster proteins may be regulated by estrogen and progesterone.

Multiple model parameters of intravoxel incoherent motion in differentiation of stage endometrial carcinoma and endometrial polyp / 中国医学影像技术

Objective: To investigate the value of the multiple model parameters of intravoxel incoherent motion (IVIM) in identification of stage endometrial carcinoma (EC) and endometrial polyp (EP). Methods: The clinical and imaging data of 31 patients with stage EC (group EC) and 14 patients with EP (group EP), confirmed by postoperative pathological examination, were retrospectively analyzed, all patients were performed on 1.5T MR (including IVIM sequence, b=0, 20, 50, 100, 150, 200, 400, 800, 1 200, 2 000, 3 000 s/mm2) before operation. The IVIM multi-model parameter values of the lesions were measured and compared between the two groups, including the standard apparent diffusion coefficient (ADC-stand), slow-apparent diffusion coefficient (ADC-slow), fast-apparent diffusion coefficient (ADC-fast), perfusion fraction (f), distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α). The ROC curve was used to evaluate the differential diagnostic efficacy of IVIM parameters for stage EC and EP. Results: The ADC-stand value, ADC-slow value, f-value, DDC value and α value of the EC group were all less than the EP group, and the ADC-fast value was greater than the EP group (all P=0.001). ROC curve results showed the standard ADC value, ADC-slow value, ADC-fast value, f value, DDC value and α value had differential diagnostic value for stage EC and EP, the AUC was 0.885, 0.877, 0.919, 0.926, 0.906 and 0.902, respectively (all P<0.05). Conclusion: The multi-model parameters of IVIM sequence can effectively identify stage EC and EP.

[Microcystic, elongated and fragmented invasion pattern in endometrial carcinoma: the clinicopathology analysis].

Objective: To assess the clinical value for the clinicopathological features of microcystic elongated and fragmented (MELF) invasion in endometrial carcinoma (EEC) . Methods: The clinicopathological data of 108 cases of endometrial carcinoma with total hysterectomy, bilateral adnexectomy, and pelvic dissection were retrospectively analysis in Peking University People's Hospital from April 2015 to October 2016. Twenty-five patients with endometrial carcinoma showing MELF invasion pattern were collected. We analyzed retrospectively the association of MELF pattern invasion with clinical pathology data and prognosis of the patients, partial immunohistochemical staining was implemented. MELF invasion was a special invasion pattern and characterized by microcystic, elongated, fragmented (composed of cluster cells) gland in muscular layer. Results: The incidence rate was 23.1% (25/108). These patients mean age was (59.3±10.9) years old. Four cases were premenopausal, and 21 were postmenopausal. Abnormal vaginal bleeding was the main clinical presentation. The lesions tend to appear adjacent to the tumor body. Sometimes, it may be appears away from the tumor body in the deep muscle layer.Lymph node metastasis were present in 5 cases (20%, 5/25). Thirteen cases (52%, 13/25) of them demonstrated lymph vascular space involvement (LVSI). The immunohischemical expression of ER,PR, Ki-67 and galectin-3 showing MELF invasion pattern were weaker than no showing MELF invasion pattern endometrial carcinoma, cktokeratin (CK) was showed diffuse strong positive expression, E-cadherin was moderately positive expression. All 25 cases were followed up for (23.2±5.9) months (14-33 months) after the therapy with no recurrence on metastasis. Conclusions: MELF invasion pattern is a special invasion pattern in low-grade EEC. The incidence of LVSI and lymph node metastasis rate in endometrial carcinoma with MELF invasion are significantly increased. The prognosis of MELF invasion pattern may be poor.

[Clinicopathologic and survival analysis of synchronous primary endometrial and ovarian cancer].

Objective: To demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary endometrial and ovarian cancer (SEOC) . Methods: A retrospective analysis of 63 pathologically proven cases of SEOC diagnosed in Peking Union Medical College Hospital from January 2000 to May 2018 was carried out. Results: (1) Clinical features: mean age at diagnosis was (48.3±10.0) years, and the mean body mass index (BMI) was (23.4±3.7) kg/m(2). The most common presenting symptom was abnormal uterine bleeding with a ratio of 73% (46/63). Forty-three patients (68%, 43/63) were premenopausal, and 30% (19/63) were nulliparous. (2) Pathological features: for the endometrial cancer, 90% patients were diagnosed at stage Ⅰ, and 81% were low grade tumors (G(1)-G(2)). The histological type of endometrial cancer was mainly endometrioid carcinoma (86%) and majority (81%) of patients were proved without or with superficial myometrial invasion. For the ovarian cancer, 70% patients were diagnosed at stage Ⅰ and 65% were low grade tumors (G(1)-G(2)). Sixty-two percent of ovarian cancers were endometrioid carcinoma and 68% of patients had unilateral involvement of the ovaries. (3) Treatment and prognosis: all patients underwent surgery, of which 56 (89%) underwent staging surgery including retroperitoneal lymphadenectomy, and 57 (90%) received postoperative adjuvant therapy. The median follow-up time was 48.0 months (range, 2-176 months) , and 13% of the patients experienced tumor recurrence during the follow-up period. The median time to recurrence was 38.5 months, and 6 patients (10%) died of tumor recurrence. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) for all patients were 69% and 80%, respectively. (4) Prognostic factors: univariate analysis showed that the presence of lymphovascular space invasion (LVSI) , non-endometrioid histology of ovarian cancer and stage of ovarian cancer above stage Ⅰ were associated with significantly worse PFS (P<0.05). LVSI, high grade of endometrial cancer, and above stage Ⅰ of ovarian cancer were associated with significantly worse OS (P<0.05). On multivariate analysis, LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stage Ⅰwere associated with significantly worse PFS (P<0.05). In addition, LVSI and stage of ovarian cancer above stage Ⅰ were also associated with significantly worse OS (P<0.05) . Conclusions: Women with SEOC are young, premenopausal and have a favorable overall prognosis. Presence of LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stage Ⅰ are independent prognostic factors for PFS, and stage of ovarian cancer above stage Ⅰare independent prognostic factors for OS.

Value of combined adjuvant chemotherapy and radiation on survival for stage III uterine cancer: is less radiation equal to more?

OBJECTIVE: Locally advanced endometrioid adenocarcinoma (LA-EAC) accounts for the majority of deaths for this cancer, yet there is no consensus on adjuvant treatment after surgery. Past studies suggest that combined modality treatment (CMT) may improve outcomes over treatment with chemotherapy (CT) or radiation therapy (RT, either external beam radiotherapy [EBRT] or vaginal brachytherapy [VBT]) alone. Using a large US-based population-based registry, we evaluated adjuvant CMT in LA-EAC and the relative benefit of regional EBRT compared to focused VBT. METHODS: We studied patients diagnosed with Stage III LA-EAC between 2004 and 2013 from the National Cancer Data Base (NCDB). We used Cox regression and a log-rank test to assess survival based on treatment with CT alone, EBRT alone, VBT alone, or CMT with EBRT and/or VBT. We used a χ² test to compare covariates between patients receiving CMT with EBRT or VBT. RESULTS: Patients who received CMT had better survival than those who received CT or EBRT/VBT alone. Compared to CMT with VBT, patients who received CMT with EBRT were slightly older and had more advanced-stage or positive nodes, and fewer had lymph node surgery. We found no survival difference between CMT with EBRT and CMT with VBT even when categorizing patients as high or low risk according to age, grade, and stage (low-risk p=0.3460; high-risk p=0.2158). CONCLUSION: CMT was associated with superior survival outcomes compared to monotherapy. We observed no survival difference between radiation modalities in CMT, which highlights the effectiveness of a more focused treatment like brachytherapy.

Myoferlin Expression and Its Correlation with FIGO Histologic Grading in Early-Stage Endometrioid Carcinoma.

BACKGROUND: For endometrioid carcinoma patients, International Federation of Gynecologists and Obstetricians (FIGO) histologic grading is very important for identifying the appropriate treatment method. However, the interobserver discrepancy with this three-tiered grading system is a serious potential problem. In this study, we used immunohistochemistry to analyze the relationship between FIGO histologic grading score and myoferlin expression. METHODS: We studied the endometrioid carcinoma tissues of 60 patients from Gyeongsang National University Hospital between January 2002 and December 2009. Immunohistochemical analysis of myoferlin was performed on tissue microarray blocks from surgical specimens. RESULTS: Myoferlin expression was observed in 58 of 60 patients. Moderate and strong myoferlin expression was observed in low-grade endometrioid carcinoma, while there was a tendency toward loss of myoferlin expression in high-grade endometrioid carcinoma (p<.001). CONCLUSIONS: Our study revealed that myoferlin loss is significantly correlated with high FIGO grade of endometrioid carcinoma.