Fas/FasL和Bcl-2在人乳腺癌组织中的表达及其与浸润淋巴细胞的关系

Expression of Fas, FasL, Bcl-2 and its relation with lymphocytes in human breast cancer

目的通过观察乳腺癌组织中凋亡调节蛋白Fas、FasL、Bcl-2的表达及其与肿瘤浸润淋巴细胞(TIL)的关系,探讨Fas、FasL、Bcl-2与乳腺癌发生、发展的关系,为乳腺癌的生物治疗提供实验依据。方法收集手术切除的人乳腺癌组织和癌旁相对正常乳腺组织。用免疫组织化学方法和图像分析技术对21例乳腺癌标本进行检测。结果乳腺癌组织中Fas的阳性表达率明显低于相对正常乳腺组织(P<0.05),且淋巴细胞浸润性乳腺癌组织中Fas的阳性表达明显低于非浸润性乳腺癌组织(P<0.05);乳腺癌组织中FasL、Bcl-2的阳性表达率明显高于相对正常乳腺组织(P<0.05),且淋巴细胞浸润性乳腺癌组织明显高于非淋巴细胞浸润性乳腺癌组织(P<0.05);乳腺癌组织中Fas阳性淋巴细胞的数量与相对正常乳腺组织相比明显增多(P<0.05);乳腺癌组织Bcl-2阳性淋巴细胞的数量与相对正常乳腺组织相比明显减少(P<0.05)。结论①乳腺癌组织中Fas表达下调和FasL的过度表达,逃避了免疫监视,诱导Fas敏感的TIL凋亡,从而导致肿瘤的生长;②乳腺癌组织中癌基因Bcl-2过度表达及Bcl-2阳性淋巴细胞的低表达,使肿瘤抗凋亡机制过度激活,肿瘤细胞对Fas/FasL易感性较淋巴细胞相对低,导致TIL死亡,而不是肿瘤细胞死亡。

Objective To investigate the expression of Fas, FasL, Bcl-2 and its relation with lymphocytes in human breast cancer tissues, and discuss the relation between Fas, FasL, Bcl-2 and developing of breast cancer. The study can provide the experimental data in the further biological therap of breast cancer. Methods The human breast cancer tissues and relatively normal breast tissue were collected from surgical operation and the samples of 21 patients with breast cancer were analyzed by immunocytochemistry and computer imaging techniques. Results The result showed that the expression rate of Fas was low in breast cancer tissues than those of relatively normal breast tissues（P〈0.05）, and the expression rate of Fas was low in breast cancer tissues with high lymphoid infiltration than those of no lymphoid infiltration （P〈0.05）. The expression rate of FasL, Bcl-2 was high in breast cancer tissues than those of relatively normal breast tissues（P〈0.05）, and the expression rate of FasL, Bcl-2 was high in breast cancer tissues with high lymphoid infiltration than those of no lymphoid infihration（P〈0.05）. The number of Fas＋lympbocytes increase greatly with significance（P〈0.05）. The number of Bcl-2^＋ lymphocytes reduced greatly with significance （P〈0.05）. Conclusion ①The expression of Fas was reduced and the expression of FasL was increased in breast cancer, which escaped immune surveillance, induced sensitive TIL of Fas apoptosis. As a result, these can lead cancer grow. ②Tbe expression of Bcl-2 was increased in breast cancer and the expression of Bcl-2^＋ lymphocytes was reduced in breast cancer, which can active the Anti-apoptotic mechanism of breast cancer, susceptibility, of cancer cells to Fas/FasL is lower than that of lymphocytes, and cause of death of TIL rather than cancer cells.