Application value of CT texture analysis for evaluating Ki-67 expression in patient with esophageal squamous cell carcinoma / 实用放射学杂志

Objective To explore the application value of CT texture analysis for evaluating Ki-67 expression in patient with esophageal squamous cell carcinoma.Methods Sixty-one cases of pathologically confirmed esophageal squamous cell carcinoma patients were selected to obtain the Ki-67 protein expression status of the patients'pathological tissues,and the patients were divided into a high-expression group and a low-expression group.All patients underwent plain and enhanced chest CT within two weeks before surgery.Lesions delineation and texture feature extraction of esophageal cancer were obtained via Omni-Kinetics software.The texture parameters included Min Intensity,Max Intensity,Median Intensity,Mean Intensity,Deviation,Skewness,Kurtosis,Entropy,Energy,Correlation,Haralick,short run high grey level emphasis(SRHGLE),short run low grey level emphasis(SRLGLE),long run high grey level emphasis(LRHGLE),long run low grey level emphasis(LRLGLE),Grey Level Nonuniformity,Run Length Nonuniformity.The differences of texture features among different Ki-67 expression groups were compared,and the receiver operating characteristic(ROC)curve was used to analyze the predictive value of Ki-67 expression in patient with esophageal cancer.Results In plain CT images,the SRHGLE and Grey Level Nonuniformity of the high expression group were significantly higher than those of the low expression group(P=0.010,0.002,respectively).In enhanced CT images,the Mean Intensity,Entropy and Grey Level Nonuniformity of the high expression group were significantly higher than those of the low expression group(P=0.026,0.037,0.001,respectively),and SRHGLE and LRHGLE of the high expression group were significantly lower than those of the low expression group(P=0.016,0.010,respectively).The area under the curve(AUC)of texture features in plain CT were 0.676-0.740,and the AUC of combined diagnosis reached 0.770[95%confidence interval(CI):0.645,0.868],and sensitivity and specificity was 0.921,0.565,respectively.In enhanced CT,the AUC of texture features were 0.629-0.750,the AUC of combined diagnosis increased to 0.903(95%CI:0.799,0.964),and sensitivity and specificity was 0.816,0.826,respectively.Conclusion CT texture analysis can early and non-invasively predict Ki-67 expression in patient with esophageal squamous cell carcinoma,it can be used as an imaging marker to evaluate the proliferative activity of esophageal cancer cells,and may provide diagnosis and treatment information for clinical decision-making of esophageal squamous cell carcinoma.

Prediction of Ki-67 expression status in breast cancer based on ultrasound radiomics combined with clinicopathologic features / 中华超声影像学杂志

Objective:To investigate the prediction of the tumor proliferation antigen(Ki-67) expression status in breast cancer patients based on ultrasound radiomics combined with clinicopathologic features.Methods:Breast cancer patients who underwent 2D ultrasound and Ki-67 examination from January 2018 to February 2022 in Changzhou Second People′s Hospital, Nanjing Medical University were retrospectively analyzed. Among them, 427 patients from Chengzhong campus were randomly divided into training and validation sets in the ratio of 8∶2, and 229 patients from Yanghu campus were used as an independent external test set. Radiomics features were extracted from the region of interest of 2D ultrasound images, and the Mann-Whitney U test, recursive feature elimination, and minimum absolute shrinkage and selection operators were used to perform feature dimensionality reduction and to establish a radiomics score(Rad-score). Subsequently, single/multifactor logistic regression regression analyses were used to construct a joint prediction model based on Rad-score and clinicopathological features. Model performance and utility were assessed using the subject operating characteristic area under the curve (AUC), calibration curve, and decision curve analyses. Results:The AUCs of the joint model for predicting Ki-67 expression status in breast cancer in the training, validation, and test sets were 0.858, 0.797, and 0.802, respectively, which were superior to those of the radiomics (0.772, 0.731, and 0.713) and clinical models (0.738, 0.750, and 0.707). Calibration curve and decision curve analyses indicated that the joint model had good calibration and clinical value.Conclusions:A joint model based on ultrasound radiomics and clinicopathological features can effectively predict the Ki-67 expression status of breast cancer, which is expected to become a non-invasive tool for Ki-67 detection and provide clinicians with an important auxiliary diagnostic and therapeutic decision-making basis.

The expression and clinical significance of TTLL12 in hilar cholangiocarcinoma / 中华肝胆外科杂志

Objective:To analyze the expression of tubulin-tyrosine ligase-like 12 (TTLL12) in hilar cholangiocarcinoma and its adjacent tissues, and to explore the relationship between TTLL12 and clinicopathological features and prognosis of patients with hilar cholangiocarcinoma.Methods:The carcinoma tissues and paracancerous tissues of 45 patients with hilar cholangiocarcinoma who had been operated in Qingdao Municipal Hospital from January 2016 to December 2020 were collected to prepare paraffin sections, including 27 males and 18 females, aged (58.8±8.5) years. The expression of TTLL12 and Ki-67 was detected by immunohistochemical staining. According to TTLL12 expression in cancer tissues, 45 patients were divided into negative group ( n=15) and positive group ( n=30). The relationship between TTLL12 positive expression and clinicopathological features such as lymph node metastasis and tumor differentiation was analyzed. The correlation between TTLL12 and Ki-67 expression in cancer tissues was analyze by Spearman correlation analysis. Kaplan-Meier method was used for survival analysis, and log-rank test was used to compare the survival rate. Results:Immunohistochemical staining showed that the expression of TTLL12 and Ki-67 in 45 patients with hilar cholangiocarcinoma was significantly higher than that in paracancerous tissues. The expression of TTLL12 in hilar cholangiocarcinoma was positively correlated with that of Ki-67 (correlation coefficient was 0.601, P<0.001). The positive expression rates of TTLL12 and Ki-67 in 45 cases of hilar cholangiocarcinoma were 66.7% (30/45) and 77.8% (35/45), respectively, which were higher than those in adjacent tissues 11.1% (5/45) and 15.6% (7/45), and the differences were statistically significant ( χ2=11.25, 29.01, both P<0.001). The positive expression of TTLL12 and Ki-67 in hilar cholangiocarcinoma was correlated with lymph node metastasis and tumor differentiation (all P<0.05). The median overall survival time was 44 months in TTLL12 negative group and 21 months in TTLL12 positive group. The 5-year survival rate of TTLL12 carcinoma tissue negative expression group was 33.1%, which was better than that of TTLL12 carcinoma tissue expression positive group (18.3%), and the difference was statistically significant ( χ2=6.12, P=0.013). Conclusions:The expression of TTLL12 in hilar cholangiocarcinoma was higher than that in paracancerous tissues, and there was a positive correlation between TTLL12 and Ki-67 in carcinoma tissues. The positive expression of TTLL12 is closely related to tumor differentiation, lymph node metastasis and poor prognosis of patients. TTLL12 may be a marker for predicting the prognosis of patients with hilar cholangiocarcinoma.

Value of radiomics signatures based on 18F-FDG PET/CT for predicting molecular classification and Ki-67 expression of breast cancer / 中华核医学与分子影像杂志

Objective:To investigate the value of radiomics signatures based on 18F-FDG PET/CT for predicting molecular classification and Ki-67 expression of breast cancer. Methods:A total of 134 female patients ((55.4±13.3) years) who underwent 18F-FDG PET/CT examination and were diagnosed with breast cancer by pathology in the First Affiliated Hospital of Soochow University from April 2016 to May 2023 were retrospectively enrolled. LIFEx software was used to extract radiomics features and the least absolute shrinkage and selection operator (LASSO) algorithm and independent-sample t test were used to screen potentially meaningful features and calculate the radiomics score, which were considered as radiomics models. Clinical characteristics were selected by supervised logistic regression and clinical models were established. Radiomics features and clinical characteristics were incorporated to logistic regression analysis to establish combined models. ROC curves were drawn and the differences among AUCs were analyzed by Delong test. Results:Among 134 patients, 22 were with triple negative breast cancer (TNBC), 47 were human epidermal growth factor receptor 2 (HER2) over-expression type, 37 were Luminal A type and the rest 28 were Luminal B type. The expression of Ki-67 was high in 85 patients, and was low in the rest 49 patients. The AUCs (95% CI) of the combined models for predicting TNBC, HER2 overexpression type, Luminal A type and Ki-67 expression were 0.843(0.770-0.900), 0.808(0.723-0.876), 0.825(0.711-0.908) and 0.836(0.762-0.894), respectively, which were higher than those of clinical models ( z values: 1.97-3.06, all P<0.05). Conclusion:The predictive model combining radiomics signatures based on 18F-FDG PET/CT and clinical characteristics can well predict the molecular classification and Ki-67 expression level of breast cancer.

Correlation between Ki-67 expression in tumor tissue and ultrasound features of patients with mass breast cancer / 新乡医学院学报

Objective To analyze the correlation between Ki-67 expression in tumor tissue and ultrasound features of patients with mass breast cancer.Methods A total of 90 patients(90 masses)with mass breast cancer admitted to Xinxiang Central Hospital from January 2020 to December 2022 were selected and divided into the Ki-67 high expression group(n=53)and Ki-67 low expression group(n=37)according to the expression of Ki-67 in tumor tissue.The qualitative and quantitative characteristics of contrast-enhanced ultrasound(CEUS),shear wave elastography(SWE)and color doppler flow imaging(CDFI)were compared between the two groups,and their correlation with Ki-67 expression in patients with mass breast cancer was analyzed by multivariate logistic regression.Results The proportion of CEUS perfusion defects patients in the Ki-67 high expression group was significantly higher than that in the Ki-67 low expression group(P＜0.05).There was no significant difference in CEUS margin,homogeneity,enhancement level,post-enhancement lesion range and direction between the two groups(P＞0.05).The maximum intensity,rise time,and half time in the Ki-67 high expression group were significantly higher than those in the Ki-67 low expression group(P＜0.05).There was no significant difference in arrival time,time to peak,and mean transit time between the two groups(P＞0.05).The proportion of hard ring signs in SWE of patients in the Ki-67 high expression group was significantly higher than that in the Ki-67 low expression group(P＜0.05),while there was no significant difference in the proportion of SWE black hole signs between the two groups(P＞0.05).The elastic modulus ratio between lesions to surrounding parenchyma of patients in Ki-67 high expression group was higher than that in the Ki-67 low expression group(P＜0.05).There was no significant difference in the maximum,average,and minimum elastic modulus between the two groups(P＞0.05).In the Ki-67 high expression group,the proportion of patient where tumor size under CDFI was 2-5 cm,and the proportion of patients with burrs on the lesion edge were higher than those in the Ki-67 low expression group(P＜0.05).There was no significant difference in the shape,location and calcification of the lesions under CDFI between the two groups(P＞0.05).Perfusion defect,hard ring sign and edge burr were associated with high Ki-67 expression in patients with mass breast cancer(P＜0.05).Conclusion Ultrasonographic features of mass breast cancer can predict Ki-67 expression.Perfusion defect,hard ring sign,and edge burr are related to Ki-67 positive expression.

Mechanism of Ki-67 in lung cancer and related progress in research on radiomics / 中国医科大学学报

Radiomics is a new diagnostic and treatment technology,which can be employed to extract high-throughput radiomics features from CT,MR,and PET images and screen features closely related to diagnostic and treatment purposes,so as to accurately predict tumor or disease classification,prognosis,or genomic changes.Ki-67 is a type of nuclear protein,which is present only in nuclei of proliferative and dividing cells but not in those of quiescent phase cells;hence,it can be used as a predictor of cell proliferation and has been proven to be closely related to prognosis of lung cancer.This article reviews the mechanism and progress in radiomics research related to Ki-67 in lung cancer.

Analysis on correlation between PDK 1 and Ki-67 expression levels with survival and prognosis of patients with ovarian serous carcinoma / 重庆医学

Objective To analyze the relationship between the expression levels of pyruvate dehydro-genase kinase 1(PDK 1)and Ki-67 with the survival and prognosis of the patients with ovarian serous carci-noma(OSC).Methods The cancer tissues of 93 patients with OSC treated by surgery in this hospital from January 2000 to June 2020 were collected,and the expression levels of PDK1 and Ki-67 in the tissues were de-tected by immunohistochemistry.The relationship between the expression levels of PDK1 and Ki-67 with the clinicopathological characteristics of the patients with OSC was analyzed by the single factor and binary logis-tic regression model.The relationship between the PDK1 and Ki-67 expression levels with the recurrence and platinum resistance within 3 years was analyzed.The Kaplan-Meier survival curve was adopted to analyze the effect of PDKI and Ki-67 expression levels on the survival and prognosis in the patients with OSC.Results The expression levels of PDK1 and Ki-67 were related with the International Federation of Gynecology and Obstetrics(FIGO)stage,tissue differentiation level,lymphatic metastasis,ascites formation and positive asci-tes(P＜0.05).The high expression of PDK1 was a risk factor for the late FIGO stage(Ⅲ-Ⅳ),lymphatic metastasis and ascites positive in the patients with OSC(P＜0.05);the high expression of Ki-67 was a risk factor for the late FIGO stage(Ⅲ-Ⅳ)and ascites formationin in the patients with OSC(P＜0.05).The re-currence rate and platinum resistance rate within 3 years in the patients with PDKi and Ki-67 high expressions were significantly higher than those in the patients with low expressions(P＜0.05).The progression-free survival(PFS),overall survival(OS)and 5-year survival rate in the patients with high PDK1 and Ki-67 ex-pressions were significantly lower than those in the patients with low expressions(P＜0.05).Conclusion The expression levels of PDK 1 and Ki-67 play an important role in judging the survival and prognosis of the patients with OSC.

Combined detection of PAX1 methylation and p16/Ki-67 dual staining improves diagnostic performance for atypical squamous cells in cervical cancer / 陆军军医大学学报

Objective To compare paired boxed gene 1(PAX1)methylation and p16/Ki-67 double staining alone and in combination in thinprep cytologic test(TCT)for distinguishing atypical squamous cells of undetermined significance(ASC-US)and low-grade squamous intraepithelial lesion(LSIL)population.Methods A total of 247 patients with TCT results of ASC-US and LSIL admitted in our hospital from January 2021 to December 2022 were enrolled in this study.Detection efficacy of PAX1 methylation and p16/Ki-67 double staining alone and in combination was evaluated with colposcopic pathologic results as the gold standard and the sensitivity,specificity,accuracy and area under the curve(AUC)as evaluation indexes.Results The positive rates of PAX1 methylation and p16/Ki-67 double staining were increased with the severity of pathological findings.Combined detection of PAX1 methylation and p16/Ki-67 assay had a sensitivity of 91.25％,specificity of 97.72％and accuracy of 95.51％in the women with TCT of ASC-US,and these values were statistically better than those of PAX1 methylation and p16/Ki-67 double staining alone(P＜0.01).Conclusion The combination of PAX1 methylation and p16/Ki-67 double-staining assay can further improve the diagnostic efficacy in patients with ASC-US on TCT results.

Expression and prognostic factors analysis of CYFRA21-1, CEA, and Ki67 in non-small cell lung cancer / 中国胸心血管外科临床杂志

@#Objective To explore the value of preoperative detection of soluble fragments of cytokeratin-19 (CYFRA21-1), carcinoembryonic antigen (CEA), and postoperative detection of nuclear proliferation associated antigen Ki67 in prognostic evaluation of non-small cell lung cancer patients. Methods The clinicopathological data and follow-up results of patients with non-small cell lung cancer treated in the Department of Thoracic Surgery of the First Affiliated Hospital of Xiamen University in 2017 were collected. CYFRA21-1>3.39 ng/mL was defined as positive, and CEA>5 ng/mL was defined as positive. The receiver operating characteristic curve (ROC curve) of Ki67 expression level was drawn. The maximum area under the curve (AUC) was the cutoff value of Ki67 expression level, and the Ki67 expression level greater than its cutoff value was defined as positive. Cox regression analysis was used to determine the independent risk factors for poor prognosis in patients with non-small cell lung cancer. Results Finally 248 patients were collected, including 125 males and 123 females, with a median age of 61 years (ranging from 30 to 81 years) at the time of surgery. Univariate analysis showed that positive CYFRA21-1, high expression of Ki67, positive CEA, age≥60 years at operation, distant metastasis, lymph node metastasis, maximum tumor diameter>3 cm, and TNM stage Ⅲ were associated with poor prognosis in patients with non-small cell lung cancer. When combined detection of preoperative tumor markers and postoperative Ki67, the prognosis of all negative patients was the best, and that of all positive patients was the worst. Cox regression analysis showed that positive CEA+positive CYFRA21-1+high expression of Ki67 was an independent risk factor for poor prognosis in patients with non-small cell lung cancer (P<0.05). Conclusion The combined detection of preoperative serum CYFRA21-1, CEA, and postoperative Ki67 has important value in evaluating the prognosis of non-small cell lung cancer patients.

Clinicopathological features and prognosis analysis of salivary duct carcinoma / 口腔疾病防治

Objective@#To summarize the clinicopathological characteristics and prognostic factors of salivary duct carcinoma (SDC) patients.@*Methods@#This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. The clinical data of 30 SDC patients who were admitted to the Fourth Hospital of Hebei Medical University from 2014 to 2022, including case records, pathological diagnoses, immunohistochemical indicators, treatment methods, follow-up data, and other data, were retrospectively analyzed. SPSS 26.0 software was used to process the data and construct relevant curves. The chi-square test was used to analyze the correlation between different immunohistochemical indices and the recurrence and metastasis of SDC, and a single factor was used to analyze clinical prognostic factors.@*Results@#Among the 30 SDC patients, the male-to-female ratio was 5∶1, with a median age of 61.5 years. Approximately 60% of cases occurred in the parotid gland, whereas the remainder occurred in the submaxillary gland, sublingual gland, or minor salivary gland. Among them, 19 patients were androgen receptor-positive, 23 patients were human epidermal growth factor receptor-2 positive, and 26 patients were Ki-67 positive. Postoperative follow-up was 18-94 months, with a median follow-up of 37 months. There were 13 cases of recurrence and 14 cases of distant metastasis. The 5-year overall survival rate was only 31.2%. The long-term survival of patients who underwent postoperative radiotherapy and chemoradiotherapy was better than that of patients who underwent surgery alone (P= 0.027). T stage and lymph node invasion were associated with prognosis and survival (P<0.05). There was a correlation between a Ki-67-positive cell count ≥ 40% and postoperative recurrence or metastasis (P = 0.025).@*Conclusion@#Radical surgery combined with postoperative radiotherapy and chemoradiotherapy is helpful for improving long-term overall survival, and tumor T stage and lymph node metastasis may be the main factors affecting the prognosis of patients with SDC. Patients with Ki-67-positive cell counts ≥ 40% are prone to postoperative recurrence or metastasis.

Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study

ABSTRACT BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.

The association of BRAF V600E gene mutation with proliferative activity and histopathological characteristics of congenital melanocytic nevi in children

Abstract Background: A lot of congenital melanocytic nevi (CMN) carry the somatic mutation in the oncogene BRAF V600E. But the detailed histopathologic characteristics and the proliferative activity of CMN with BRAF V600E gene mutation have not been systematically documented. Objective: To identify the proliferative activity and histopathological features correlating them with BRAF V600E gene mutation status in CMN. Methods: CMN were retrospectively identified from the laboratory reporting system. Mutations were determined by Sanger sequencing. The CMN were divided into a mutant group and control group according to whether there was BRAF gene mutation and were strictly matched according to gender, age, nevus size, and location. Histopathological analysis, analysis of Ki67 expression by immunohistochemistry and laser confocal fluorescence microscopy were performed. Results: The differences in Ki67 index, the depth of nevus cell involvement and the number of nevus cell nests between the mutant group and the control group was statistically significant, with p-values of 0.041, 0.002 and 0.007, respectively. Compared with BRAFV600E negative nevi, BRAF V600E positive nevi often exhibited predominantly nested intraepidermal melanocytes, and larger junctional nests, but the difference in this datasets were not statistically significant. The number of nests (p = 0.001) was positively correlated with the proportion of Ki67 positive cells. Study limitations: A small sample of patients were included and there was no follow-up. Conclusions: BRAF V600E gene mutations were associated with high proliferative activity and distinct histopathological features in congenital melanocytic nevi.

Expression and sensitivity of immunohistochemical markers SMA, Desmin, CD10 for uterine leiomyomas - A tertiary care centre experience

Introduction: Leiomyoma is the most common benign tumor of the uterus which usually presents with menorrhagia, pain in abdomen or both. In extremely rare cases where uterine leiomyoma can be difficult to distinguish from other uterine smooth muscle tumors, immunohistochemistry is used. This study was aimed to study the expression and sensitivity of immunohistochemical markers SMA, Desmin, CD 10 for uterine leiomyomas and to find average number of mitosis in uterine leiomyomas using Ki 67. Materials and methods: The present study was carried out in the Department of Pathology, Dhiraj General Hospital and Smt. Bhikhiben Kanjibhai Shah Medical Institute and Research Centre, Sumandeep Vidyapeeth, Piparia. A total 50 cases of uterine leiomyomas after its histological diagnosis were evaluated with immunohistochemical markers SMA, Desmin, CD 10 and Ki 67. Results: SMA expression was seen in all 50 cases of uterine leiomyomas with strong expression in 44 cases (88%). Strong SMA expression was seen more in usual leiomyomas as compared to leiomyomas with secondary changes. Desmin expression was also seen in all the 50 cases of uterine leiomyomas with moderate expression in 26 cases (52%). Weak CD 10 expression was seen in 15 cases of uterine leiomyomas (30%). Ki 67 was expressed very focally in only 3 cases of leiomyomas with mean value of only 0.3% tumor cells. Conclusions: Leimyomas was most frequently seen in the women in 4th decade. The most common clinical presentation was menorrhagia. SMA and Desmin expression was seen in all the cases with strong and moderate immunoreactivity respectively. SMA expression was found to be more specific than Desmin in uterine leiomyoma. Weak CD 10 and focal Ki 67 were expressed only in few cases and were found to be insignificant.

The role and clinical significance of microRNA-29a-3p in the development of hypopharyngeal carcinoma

Abstract Objective MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. Methods 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. Results Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p< 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p< 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. Conclusions The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using "Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence".

Inmunolocalización de citoqueratina 14, 19 y Ki-67 en el epitelio de pacientes con agrandamiento gingival

R E S U M E N En pacientes con ortodoncia aparecen eventos patológicos no deseados como agrandamiento gingival inducido por tratamiento de ortodoncia (AGTO) o hipertrofia gingival. El objetivo del estudio es identificar la distribución inmunohistoquímica de citoqueratina CK-14, CK-19 y Ki-67 en epitelio gingival de pacientes con AGTO. Se seleccionaron I3 pacientes divididos en: grupo control (n=6), conformado por individuos periodontalmente sanos no portadores de aparatología ortodóntica y grupo test (n=7), integrado por pacientes con AGTO. Los marcadores CK-14, CK-19 y Ki-67 fueron identificados mediante inmunohistoquímica con anticuerpos monoclonales y observados en un microscopio óptico Leica DM 500. En los pacientes del grupo test el tejido epitelial se mostró hipertrófico con pérdida en la continuidad de la membrana basal. La CK-14 y CK-19 fue positiva en el epitelio de todos los sujetos evaluados, con una expresión positiva de alta intensidad en células de la lámina basal del grupo test. El promedio de células positivas para Ki-67 en el grupo test fue de 56%. En conclusión, la CK-14, CK-19 y Ki-67 son marcadores con elevada inmunoreactividad en tejido gingival de pacientes con AGTO portadores de ortodoncia.

During orthodontic treatment, unwanted pathological events such as gingival overgrowth induced by orthodontic treatment or gingival hypertrophy may appear The objective of this study is to identify immunohistochemical distribution of cytokeratin CK-14, CK-19 and Ki-67 in the gingival epithelium of patients with gingival overgrowth induced by orthodontic treatment. Thirteen patients were selected divided into: control group (n = 6), conformed of periodontally healthy individuals without orthodontic appliances and the test group (n = 7), conformed of patients with gingival overgrowth induced by orthodontic treatment. The biomarkers CK-14, CK-19 and Ki-67 were identified by immunohistochemistry with monoclonal antibodies and observed in a Leica DM 500 optical microscope. Hypertrophic epithelial tissue with loss of continuity of the basement membrane was found in the test group patients. CK-14 and CK-19 were positive in the epithelial tissue of all the subjects evaluated, with a high intensity positive expression in the cells of the basal lamina of the test group. The average number of cells positive for Ki-67 in test group was 56%. In conclusion, CK-14, CK-19 and Ki-67 are biomarkers with high immunoreactivity in the gingival tissue of patients with gingival overgrowth induced by orthodontic treatment.

Durante o tratamento ortodôntico, eventos patológicos indesejados como o crescimento gengival induzido pelo tratamento ortodôntico (CGTO) ou hipertrofia gengival podem aparecer: O objetivo deste estudo é identificar a distribuição imuno-histoquímica das citoqueratinas CK -14, CK-19 e Ki-67 no epitélio gengival de pacientes com CGTO. Foram selecionados 13 pacientes divididos em: grupo controle (n=6), conformado por indivíduos periodontalmente saudáveis sem aparelhos ortodônticos e o grupo teste (n=7), conformado por pacientes com CGTO. Os biomarcadores CK-14, CK-19 e Ki-67 foram identificados por imuno-histoquímica com anticorpos monoclonais e observados em microscópio óptico Leica DM 500. Tecido epitelial hipertrófico com perda de continuidade da membrana basal foi encontrado nos pacientes do grupo teste. CK-14 e CK-19 foram positivos no tecido epitelial de todos os sujeitos avaliados, com expressão positiva de alta intensidade nas células da lâmina basal do grupo teste. O número médio de células positivas para Ki-67 no grupo teste foi de 56%. Em conclusão, CK-14, CK-19 e Ki-67 são biomarcadores com alta imunorreatividade no tecido gengival de pacientes com CGTO.

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.

Tumor risk markers in recurrent respiratory papillomatosis

Abstract Objectives: This study aims to investigate the pattern of immunoexpression of proteins p16, p53 and Ki-67 in RRP, as well as to evaluate its influence on the number of surgeries that patients have undergone to date and to analyze the benefit of immunohistochemistry in this disease. Methods: Clinical-demographic data and tumor samples were obtained from 33 patients with RRP. The expression of proteins p16, p53 and Ki-67 was analyzed by immunohistochemical method. Results: Most patients had already undergone more than one surgery. The p16 marker was negative in 24.2% of the cases, with little positivity in 27.3% of the cases, moderate in 36.4% and intense in 12.1%. The p53 marker was positive in all cases, with little immunoexpression in 39.4% of cases, moderate in 36.4% and intense in 24.2%. The Ki-67 marker showed nuclear positivity in all lesions, although in varying degrees, with a mean proliferative index ±SD (standard deviation) of 51.7±26. Conclusions: The papillomatous lesions had varying degrees of immunoexpression of proteins p16, p53 and Ki-67, but no specific immunohistochemical pattern was observed. It was found, with statistical difference, that the number of surgeries was higher in cases with greater intensity of p53 expression, without correlation with the other markers. The benefit of immunohistochemistry in recurrent respiratory papillomatosis may lie in the prognostic assessment. However, further studies are needed to evaluate the use of this technique for this purpose. Level of evidence:: 4.

Agrandamiento gingival asociado al tratamiento de ortodoncia: análisis histológico e inmunohistoquímico de dos casos clínicos

El agrandamiento gingival asociado al tratamiento de ortodoncia (AGTO) es el crecimiento no controlado de la encía. Aquí reportamos dos casos clínicos de pacientes masculinos sistèmicamente sanos con AGTO generalizado, con asociación a la biopelícula dental y sin esta. En ambos pacientes se identificó un tejido epitelial hiperplásico con abundantes células positivas para Ki-67 y tejido conectivo rico en fibras de colágeno distribuidas aleatoriamente. Futuros estudios serán útiles para dilucidar las diferencias fisiopatológicas del AGTO con relación con el biofilm dental y sin esta.

Orthodontic treatment-induce gingival overgrowth (OTGO) is uncontrolled growth of the gingiva. Here, we report two clinical cases of systemically healthy male patients with generalized GH undergoing orthodontic treatment, with and without association with dental biofilm. In both patients, hyperplastic epithelial tissue was identified with abundant Ki-67 positive cells and connective tissue rich in randomly distributed collagen fibers. Future studies will be useful to elucidate the pathophysiological differences of OTGO with and without relation to dental biofilm.

Evaluation of variable p16 immunostaining patterns, Ki-67 indices and HPV status in cervical SILs and squamous cell carcinomas: An institutional experience

Objective: The present study evaluates the immunoexpression of p16 and Ki-67 in cervical squamous intraepithelial lesion (SIL) and carcinomas and correlates their expression with clinicopathological features and HPV-DNA status. Material and Methods: A total 36 included cases of SIL and squamous cell carcinoma (SCC) were subjected to p16 and Ki-67 immunostaining. p16 staining was evaluated depending on grading, distribution, localization pattern, intensity and IHC score. Ki-67 expression was graded based on percentage of positive cells. Results: Incidence of HSIL and SCC cases was found to be significantly increased with parity > 5. p16 grade III diffuse nucleocytoplasmic immunostaining was observed in 62.5% LSIL, 80% HSIL and 87% SCC cases. Significant association of p16 staining intensity, IHC score and Ki-67 indices was noted with increasing grades of SILs and carcinomas. Conclusion: Our experience indicates that a combination of p16 and Ki-67 immunostaining may be useful to determine the severity of dysplastic change.