Abstract
Background: the purpose of the present study to investigate the RNA expression level of Oct4, Survivin and Cyclin D1 genes in Triple-negative breast cancer (TNBC) and compared to non-triple negative breast cancer (non-TNBC) group. Also, correlate the results of gene expression with clinicopathological features of patients. Method, RNA expression levels of Oct4, Survivin and Cyclin D1 was tested for 100 breast cancer (BC) patients [formalin fixed paraffin embedded tissue (FFPE)] diagnosed as invasive duct carcinoma in Pathology Department, National Cancer Institute (NCI), Cairo University. The qRT-PCR technique is use and the results correlated to clinico-pathological characteristics of patients and survival rates. Result, in (TNBC) patients, oct4, survivin and cyclin D1 showed positive expression in 30 (60%), 32(64%) and 32 (64%) (p < 0.001, p= 0.001 and p= 0.003;respectively). In non-TNBC patients, the positive expression of oct4, survivin and cyclin D1 gene was 11(22%), 15(30%) and 17(34%) (p < 0.001, p= 0.001 and p= 0.003;respectively). All patients in TNBC have negative ER, PR and HER-2 receptor (p=0.001). There was highly statistically significant difference between oct4 gene expression and all the clinico-pathological features except the family history. A significant difference between cyclin D1gene expression and all the clinico-pathological features except the tumor size, tumor grade and lymphnode status. Statistically difference was found between survivin gene expression and all the clinico-pathological features except the menopause state, tumor stage and tumor grade. Triple negative breast cancer patients showed significantly decreased DFS (p < 0.001, log rank) and OS (p= 0.002, log rank) when compared to those with non-TNBC patients. In TNBC group, patients with positive expression of survivin was significantly associated with decreased OS (p= 0.03, log rank). TNBC tumors with positive oct4 and cyclin D1 had reduced OS compared to those negative to oct4 and cyclin D1 but without significant difference (p= 0.8 and p= 0.09, respectively, log rank). In non-TNBC group, with positive oct4, cyclin D1 and survivin did not significantly differ in terms of DFS and OS when compared to those with negative expression. Conclusion: Oct4 and survivin expression gene are better marker used for diagnosis in TNBC and for molecular targeting therapy of TNBC treatment. Cyclin D1 expression used as a marker for aggressive TNBC. The TNBC tumor possibly respond to treatment that downregulates cyclin D1 amplifica tion. More studied and large sample size is needed.
Highlights
Breast is a heterogenous disease composed of different molecular subtypes that differ in patterns of gene expression, clinical features, response to treatment, and prognosis Munjal K et al, (2009) and Curtis C et al, (2012)
RNA expression levels of Oct4, Survivin and Cyclin D1 was tested for 100 breast cancer (BC) patients [formalin fixed paraffin embedded tissue (FFPE)] diagnosed as invasive duct carcinoma in Pathology Department, National Cancer Institute (NCI), Cairo University
In Triple-negative breast cancer (TNBC) group, patients with positive expression of survivin was significantly associated with decreased overall survival (OS) (p= 0.03, log rank)
Summary
Breast is a heterogenous disease composed of different molecular subtypes that differ in patterns of gene expression, clinical features, response to treatment, and prognosis Munjal K et al, (2009) and Curtis C et al, (2012). Triple negative breast cancer (TNBC) tumors are responsive to a wide range of chemotherapeutic agents, majority of patients are more likely to develop recurrence during the first three years after treatment Kaplan, H.G. et al, (2009) with predominance of visceral and central nervous system metastases Liedtke, C.et al, (2008). TNBC is essential, there are incomplete overlap in immunohistochemistry determine it, molecular analysis to basal-like breast cancer and the mutation of BRCA1 that correlated with breast cancer. In this study, they reported that about 80% of TNBC have a basal-like molecular profile Weigelt et al, (2010a)
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