Zhang G J, Kimijima I, Watanabe T, Kanno M, Sagara H, Furukawa Y, Tsuchiya A, Abe R
Dept. of Surgery 2, Fukushima Medical College.
Gan To Kagaku Ryoho. 1998 Apr;25 Suppl 3:415-21.
Apoptosis is considered to play a critical role in tumorigenesis. It has been shown that apoptosis is controlled by both pro-oncogenes bcl-2, c-myc and tumor-suppressor genes p53. We determined the apoptotic index (AI) on light microscopy and detected immunohistochemically the expression of bcl-2 and p53 in patients with breast cancer. The correlations between AI and clinicopathological factors, bcl-2 and p53 were also analyzed. Our results showed that bcl-2 expression was down-regulated in the process from normal breast epithelial cells to intraductal carcinoma and from intraductal carcinoma to invasive carcinoma. We failed to detect p53 protein in normal breast epithelial cells, and p53 positivity was 24% and 30% in intraductal and invasive cancer tissues, respectively. Moreover, AI was significantly associated with histological grade, mitotic index, and bcl-2 and p53 expression. In univariate analyses, lower AI and bcl-2 expression was significantly predictive of a better prognosis for both disease-free survival and overall survival. These results suggest that apoptosis and apoptosis-related gene (bcl-2, p53) are related to progression and prognosis in breast cancer.
细胞凋亡被认为在肿瘤发生过程中起关键作用。研究表明,细胞凋亡受原癌基因bcl-2、c-myc以及抑癌基因p53的共同调控。我们通过光学显微镜测定了乳腺癌患者的凋亡指数(AI),并采用免疫组织化学方法检测了bcl-2和p53的表达情况。同时分析了AI与临床病理因素、bcl-2和p53之间的相关性。结果显示,从正常乳腺上皮细胞到导管内癌,以及从导管内癌到浸润性癌的过程中,bcl-2表达下调。在正常乳腺上皮细胞中未检测到p53蛋白,而在导管内癌和浸润性癌组织中,p53阳性率分别为24%和30%。此外,AI与组织学分级、有丝分裂指数以及bcl-2和p53表达显著相关。单因素分析显示,较低的AI和bcl-2表达对无病生存期和总生存期均具有显著的预后预测价值。这些结果表明,细胞凋亡及凋亡相关基因(bcl-2、p53)与乳腺癌的进展及预后相关。