Circulating Tumor Cells in Breast Cancer: Correlation with Clinicopathological Parameters, Hormone Profile and MicroRNA Polymorphisms

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Abstract

Objective: Circulating tumor cells are isolated tumor cells in the peripheral blood that serve as important prognostic indicators for many kind of tumors. The study was conducted to know the rate of detection of circulating tumor cells among breast cancer patients in comparison with benign breast diseases and control subjects and to know the association between CTC positivity and various clinicopathological parameters, hormonal profile and microRNA polymorphisms.

Material and Method: In the present case control study, we included 182 healthy controls, 108 cases of benign breast disease and 114 breast carcinoma cases. Various clinicopathological details of cases were recorded. Immunohistochemistry was performed for estrogen (ER) and progesterone receptors (PR) and Her-2 neu. Circulating tumor cells were analyzed using flow cytometry (EpCAM, CK, CD45). Genotypic frequency of micro RNA polymorphisms was determined by PCR-RFLP assay.

Results: Circulating tumor cell positivity was observed in 11/114 (9.64%) breast cancer cases but absent in benign and control groups, and was significantly associated with tumor size, histologic type, tumor grade, metastasis and skin infiltration (p<0.05). Circulating tumor cell positivity did not show any correlation with the immunohistochemical profile. No significant associations between pre-miRNA genetic variations miR-196a2 C/T (rs11614913), miR-146a G/C (rs2910164) and miR-499 T>C (rs3746444) polymorphisms and circulating tumor cell positivity were observed.

Conclusion: The flow cytometry protocol for detection and molecular characterization of circulating tumor cells is a time and cost-effective technique, suitable for routine clinical use. However, more elaborate studies are needed to establish the findings as our study was limited by small sample size.

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