c-FLIP（L）在乳腺癌中表达的意义及对凋亡的调节*

目的:检测乳腺浸润性导管癌组织中c-FLIP （L）蛋白的表达，探讨c-FLIP （L）在乳腺癌中的临床病理意义，以及对乳腺癌细胞凋亡、增殖的影响。方法:收集116 例乳腺浸润性导管癌标本，应用免疫组化技术分析c-FLIP （L）与乳腺癌临床病理因素的相关性。以TUNEL标记肿瘤细胞凋亡指数，Ki-67标记增殖指数，分析c-FLIP （L）与细胞凋亡、增殖的相关性。结果:c-FLIP（L）蛋白定位于浸润性导管癌癌细胞胞浆中，ER、PR、Ki-67定位于肿瘤细胞胞核，Her-2 定位于肿瘤细胞胞膜，TUNEL染色定位于肿瘤细胞胞核。c-FLIP （L）蛋白高表达与患者低年龄（<35岁）、绝经前、未发生远处转移、较早的pTNM 分期（Ⅰ～Ⅱ期）密切相关；与家族史、手术方式、肿瘤大小、淋巴结转移、组织学分级和肿瘤复发等临床病理因素不存在显著相关性。在总病例中，ER阳性64例（55.17%），PR阳性43例（37.07%），Her-2 阳性19例（16.38%）。 c-FLIP （L）高表达与ER、PR之间存在显著相关性（P<0.05），与Her-2 表达无关。c-FLIP （L）蛋白表达与乳腺癌凋亡指数正相关（r=0.544，P<0.05），虽然呈现c-FLIP （L）表达越高增殖指数越低的趋势，但二者之间相关系数无统计学意义（r=-0.148，P>0.05）。 结论:在乳腺癌中，c-FLIP （L）阳性表达提示患者较为良好的临床预后，该因子可能直接或间接参与肿瘤细胞凋亡过程，具有进一步研究的价值。 

The Significance of c-FLIP(L) in Breast Cancer and It's Role in Apoptosis

Objective:To observe the expression of c-FLIP(L) in invasive ductal cancer and investigate the clinicopatho -logic 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-67immunohistochemistry 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-67were 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 < 35years old, premenopausal , wi thout distant metastasis, and/or wi th earl ier pTNM stages (I-П). 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 (P<0.05) and had no correlation with Her-2 sta-tus. There was a positive correlation between c-FLIP(L) expression and apoptotic index ( r=0.544 , P<0.05). 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 , P>0.05). Conclusion:The positive expression of c-FLIP(L) protein indicates good prognosis in invasive ducta cancer and may directly or indirectly participate in the progress of apoptotic signaling transduction, which requires confirmation in further studies.