Association of menopausal status, expression of progesterone receptor and ki67 to the clinical response to neoadjuvant chemotherapy in luminal breast cancer / Associação de status menopausal, expressão de receptor de progesterona e de Ki67 à resposta clínica à quimioterapia neoadjuvante no câncer luminal de mama

Abstract Objective To identify the biomarkers of response to neoadjuvant chemotherapy in early luminal breast cancer. Methods A cross-sectional study that included all patients with early or locallyadvanced luminal breast cancer submitted to neoadjuvant chemotherapy between 2013 and 2014. Demographic, clinic and pathologic data were retrieved from patient records. The expressions of the estrogen receptor (ER), the progesterone receptor (PR), and Ki67 were analyzed by immunohistochemistry (IHC). The status of the human epidermal growth factor receptor 2 (HER2) was evaluated by IHC and fluorescent in situ hybridization (FISH). Independent predictors of clinic and pathologic response were evaluated by stepwise logistic regression models and receiver operating characteristic (ROC) curve analysis. Results Out of 298 patients identified, 115 were included in the analysis. Clinical complete response (cCR) was observed in 43.4% of the patients (49/113), and pathologic complete response (pCR) was observed in 7.1% (8/115) of the patients. The independent predictors of cCR were premenopausal status (p < 0.001), low PR expression (≤ 50% versus > 50%; p = 0.048), and Ki67 expression ≥ 14% (versus < 14%; p = 0.01). Patients with cCR were more commonly submitted to breast conserving surgery (34.7% versus 7.8%; p < 0.001). Increasing cut-off points for Ki67 expression were associated with an increase in specificity and a decrease in sensitivity to identify patients with cCR. Conclusion Premenopausal status, lower PR expression and higher Ki67 expression were associated with a higher rate of cCR to neoadjuvant chemotherapy in luminal breast cancer.

Resumo Objetivo Identificar biomarcadores de resposta à quimioterapia neoadjuvante em câncer luminal de mama. Métodos Estudo transversal em que foram incluídas todas as pacientes com câncer luminal de mama em estádio inicial ou localmente avançado que foram submetidas a quimioterapia neoadjuvante nos anos de 2013 e 2014. Dados demográficos, clínicos e patológicos foram obtidos de prontuários médicos. As expressões de receptor de estrogênio (RE), de receptor de progesterona (RP), e de Ki67 foram avaliadas por imuno-histoquímica (IHQ). A expressão do receptor tipo 2 do fator de crescimento epidérmico humano (human epidermal growth factor receptor 2, HER2) foi avaliada por IHQ e hibridização in situ por imunofluorescência (HISI). Análises de regressão logística e de curva de característica de operação do receptor (COR) foram usadas para investigar fatores preditivos independentes de resposta clínica e patológica. Resultados De 298 pacientes identificadas, 115 foram incluídas na análise. Resposta clínica completa (RCc) foi observada em 43.4% das pacientes (49/113), e resposta patológica completa (RPc), em 7.1% (8/115). Os fatores preditivos independentes de RCc foram status menopausal (p < 0.001), baixa expressão de RP (≤ 50% versus > 50%; p = 0.048), e expressão de Ki67 ≥ 14% (versus < 14%; p = 0.01). Pacientes com RCc apresentaram maior probabilidade de serem submetidas a cirurgia conservadora da mama (34.7% versus 7.8%; p < 0.001). Aumento no ponto de corte para expressão de Ki67 foi associado a aumento da especificidade e redução da sensibilidade na identificação de pacientes com RCc. Conclusão Status premenopausal, baixa expressão de RP e maior expressão de Ki67 estiveram associados a maior taxa de RCc à quimioterapia neoadjuvante no câncer luminal de mama.

Immunohistochemical Expression of p53, Bcl-2, and Ki-67 Proteins in Traditional Serrated Adenomas of Colon / 대한소화기학회지

BACKGROUND/AIMS: Serrated adenomas of the colon show mixed characteristics of both hyperplastic and adenomatous polyps. Serrated adenomas are known to progress via the serrated pathway than the adenoma-carcinoma pathway. The aim of this study was to evaluate the characteristics of traditional serrated adenomas compared to hyperplastic polyps and tubular adenomas by using immunohistochemical staining for p53, Bcl-2, and Ki-67. METHODS: Age, sex, location, size and the immunoexpression of p53, Bcl-2, and Ki-67 were retrospectively analyzed in 20 traditional serrated adenomas, 20 hyperplastic polyps, and 20 tubular adenomas from January 2007 to December 2012 at The Catholic University of Korea, Yeouido St. Mary's Hospital. RESULTS: There was no difference in Bcl-2 and p53 expression between traditional serrated adenomas and hyperplastic polyps. Ki-67 Expression of traditional serrated adenomas was higher than that of hyperplastic polyps (p=0.001). Ki-67 and p53 expression was similar between traditional serrated and tubular adenomas. Bcl-2 expression of traditional serrated adenomas was lower than that of tubular adenomas (p=0.001). Regarding the expression of p53, Bcl-2, and Ki-67 in traditional serrated adenomas, there were no statistical differences among age, sex, location, and size. CONCLUSIONS: Our study suggested that Ki-67 may be helpful in distinguishing traditional serrated adenomas from hyperplastic polyps, and p53 expression may be ineffective in distinguishing between traditional serrated and tubular adenomas. From Bcl-2 expression, it is suggested that the tumorigenesis of traditional serrated adenomas is lower than that of tubular adenomas.

Immunohistochemical Expression of p53, Bcl-2, and Ki-67 Proteins in Traditional Serrated Adenomas of Colon / 대한소화기학회지

BACKGROUND/AIMS: Serrated adenomas of the colon show mixed characteristics of both hyperplastic and adenomatous polyps. Serrated adenomas are known to progress via the serrated pathway than the adenoma-carcinoma pathway. The aim of this study was to evaluate the characteristics of traditional serrated adenomas compared to hyperplastic polyps and tubular adenomas by using immunohistochemical staining for p53, Bcl-2, and Ki-67. METHODS: Age, sex, location, size and the immunoexpression of p53, Bcl-2, and Ki-67 were retrospectively analyzed in 20 traditional serrated adenomas, 20 hyperplastic polyps, and 20 tubular adenomas from January 2007 to December 2012 at The Catholic University of Korea, Yeouido St. Mary's Hospital. RESULTS: There was no difference in Bcl-2 and p53 expression between traditional serrated adenomas and hyperplastic polyps. Ki-67 Expression of traditional serrated adenomas was higher than that of hyperplastic polyps (p=0.001). Ki-67 and p53 expression was similar between traditional serrated and tubular adenomas. Bcl-2 expression of traditional serrated adenomas was lower than that of tubular adenomas (p=0.001). Regarding the expression of p53, Bcl-2, and Ki-67 in traditional serrated adenomas, there were no statistical differences among age, sex, location, and size. CONCLUSIONS: Our study suggested that Ki-67 may be helpful in distinguishing traditional serrated adenomas from hyperplastic polyps, and p53 expression may be ineffective in distinguishing between traditional serrated and tubular adenomas. From Bcl-2 expression, it is suggested that the tumorigenesis of traditional serrated adenomas is lower than that of tubular adenomas.

A cytohistological study of Ki-67 expression in ovarian tumors.

Background and Objective: The study was conducted to evaluate the diagnostic accuracy of imprint cytology in ovarian neoplasms, and to investigate the biological significance of Ki-67 antigen expression in benign and malignant ovarian tumors and correlate it with histological type, grade, and stage of malignant tumor. Materials and Methods: A total of 50 cases including 25 prospective and 25 retrospective cases were studied. Imprint cytology was performed on 25 ovarian tumors and compared with histopathological diagnosis. Ki-67 immunohistochemistry was performed on all 50 cases. Results: On immunohistochemistry, benign tumors had a mean Ki-67 index of 3.2 ± 3.7 while malignant tumors had a mean Ki-67 index of 33.1 ± 16.7, the difference being statistically significant. Significant correlation was observed between the Ki-67 index and stage of the tumor; however, there was no correlation between the grade of differentiation and histological type of tumor with the Ki-67 index. Conclusions: In the present study, the Ki-67 index was higher in advanced stage tumors; hence a higher Ki-67 index points toward the aggressive behavior and poorer clinical outcomes.

Immunohistochemical expression of ki-67 and p53 in colorectal adenomas: a clinicopathological study

To evaluate the significance of P53 and Ki-67 expression as immunohistochemical markers in early detection of premalignant changes in different types of colorectal adenomas. Also, to correlate immunohistochemical expression of the two markers with different clinicopathological parameters including; age, and sex of the patient, type, site, size and grade of dysplasia of colorectal adenomas. Forty-seven polypectomy specimens of colorectal adenomas were retrieved from the archival materials of the Gastrointestinal and Hepatic Diseases Teaching Hospital in Baghdad from 2009-2010. Four ?m section specimens were stained by immunohistochemical technique with Ki-67 and P53 tumor markers. P-values<0.05 were considered statistically significant. Immunohistochemical expressions of Ki-67 and P53 had a significant correlation with the size and grade of dysplasia in colorectal adenomas. However, there was no significant correlation among the immunohistochemical expression of Ki-67 and P53 with the age and gender of the patient, and the type and site of colorectal adenomas. There was no significant correlation between Ki-67 and P53 expressions in colorectal adenomas. Villous adenomas of colorectum showed a significant correlation with the grade of dysplasia, while there was no significant correlation between size and site of colorectal adenoma with the grade of dysplasia. High grade dysplasia with significant positive immunohistochemical markers of Ki-67 and P53 could be valuable parameters for selecting from the total colorectal adenoma population, those most deserving of close surveillance in followup cancer prevention programs. It is closely linked with increasing age particularly in patients with a large size adenoma of villous component in their histology

hTR RNA component as a marker of cellular proliferation in oral lichen planus.

Previously, we have shown that the telomerase RNA component hTR is highly expressed in the epithelium of non-dysplastic Oral Lichen Planus (OLP) lesions (11). We concluded that it is possible that this high expression might be related to the increased cellular proliferation seen in OLP rather than being an indicator of potential malignant transformation. In the present study, and in order to confirm our finding in the previous study that hTR might be a marker for cellular proliferation in OLP, we analysed OLP biopsies known to be positive for RNA component of Telomerase (hTR) for the expression of Ki-67 as a marker for cellular proliferation. Fourteen OLP tissue biopsies known to be positive for telomerase RNA component hTR, were investigated using an immunohistochemical approach to determine the rate of cellular proliferation in OLP, looking at the expression of Ki-67 protein as a marker for cellular proliferation. A statistically significant increase was found between Ki-67 expression in OLP in comparison to normal control buccal mucosa samples. The expression of hTR component in OLP might thus be a marker for cellular proliferation.

Expression of Pin1 and Ki67 in cervical cancer and their significance / 华中科技大学学报（医学）（英德文版）

In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P 0.05). The expression of Pin1 was significantly higher in adenocarcinoma than in squamous carcinoma of the uterine cervix (P < 0.05). In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P < 0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.