The significance of c-FLIP(L) in breast cancer and it's role in apoptosis

Abstract

Objective: To observe the expression of c-FLIP(L) in invasive ductal cancer and investigate the clinicopathologic significance of c-FLIP(L) and it's crucial role on apoptosis and proliferation in breast cancer cells. Methods: A total of 116 samples of primary invasive ductal cancer were selected. Immunohistochemistry was used to detect the expression of c-FLIP(L) and analyze the correlation between c-FLIP(L) protein expression and various clinicopathologic parameters. TU-NEL method was used to detect the apoptosis index (AI) and Ki-67 immunohistochemistry to detect the proliferation index (PI) of breast cancer cells. The relationships between c-FLIP(L) protein and the above indexes were statistically analyzed. Results: c-FLIP(L) staining was mainly located in the cytoplasm of breast cancer cells. ER, PR and Ki-67 were positive in the cell nucleus. Her-2 was mainly expressed in the cell membrane. TUNEL staining and apoptotic bodies were located in the cell nucleus. The clinicopathologic analyses revealed that the expression of c-FLIP(L) was significantly associated with tumor TNM stages. Furthermore, cases with highly expressed c-FLIP(L) were observed in patients who were 35 years old, premenopausal, without distant metastasis, and/or with earlier pTNM stages (I-Π). However, the expression of c-FLIP(L) was not associated with family history, operation types, tumor size (T classification), lymph node metastasis (N classification), histological grading, or recrudescence. Among all the detected samples, ER was positively expressed in 64 cases (55.17%), PR was positively expressed in 43 cases (37.07%), and Her-2 was positively expressed in 19 cases (16.38%). Still c-FLIP(L) was positive in the ER and/or PR positive cases (P0.05) and had no correlation with Her-2 status. There was a positive correlation between c-FLIP(L) expression and apoptotic index (r=0.544, P0.05). When c-FLIP(L) was highly-expressed, the proliferation index changed into low or moderate status but this did not statistically correlate (r=-0.148, P0.05). Conclusion: The positive expression of c-FLIP(L) protein indicates good prognosis in invasive ductal cancer and may directly or indirectly participate in the progress of apoptotic signaling transduction, which requires confirmation in further studies.