Yang Q, Sakurai T, Jing X, Utsunomiya H, Shan L, Nakamura Y, Nakamura M, Oura S, Suzuma T, Yoshimura G, Umemura T, Kokawa Y, Kakudo K
Department of Surgery, Affiliated Kihoku Hospital, Japan.
Pathol Int. 1999 Sep;49(9):775-80. doi: 10.1046/j.1440-1827.1999.00942.x.
Bcl-2 and Bax have been demonstrated to be associated with apoptosis in breast carcinoma, and the ratio between Bax and Bcl-2 seems to be an important determinant of cellular sensitivity to induction of apoptosis. However, little information is available on the relationship between Bcl-2, Bax and the proliferative activity of breast carcinoma. The purpose of this study was to investigate the significance of apoptosis-related genes bcl-2 and Bax and their correlation with expression of p53, tumor proliferation defined by MIB-1 expression and estrogen receptor status. Immunohistochemistry was performed to determine Bcl-2, Bax, p53, estrogen receptor (ER) and MIB-1 expression in paraffin-embedded tissues of 177 invasive breast cancers. Expression of the anti-apoptotic protein Bcl-2 was not correlated with the pro-apoptotic Bax. Bcl-2 immunostaining displayed a negative correlation with increasing histologic grade, p53 and MIB-1 (P < 0.0001, P < 0.05 and P < 0.0001, respectively) and a positive correlation with rising ER immunostaining (r = 0.305, P < 0.0001). Conversely, expression of the apoptosis-promoting protein Bax did not correlate with increasing histologic grade, p53, MIB-1 or ER status. Neither Bcl-2 expression nor Bax expression correlated with age, menopausal status, tumor size, histologic type or axillary lymph node status. These results imply that Bcl-2 is associated with good prognostic markers and the regulation of Bax is complex and does not necessarily correlate with mutant p53 status in breast cancers.
Bcl-2和Bax已被证明与乳腺癌细胞凋亡有关，Bax与Bcl-2的比例似乎是细胞对凋亡诱导敏感性的重要决定因素。然而，关于Bcl-2、Bax与乳腺癌增殖活性之间的关系，目前所知甚少。本研究的目的是探讨凋亡相关基因bcl-2和Bax的意义及其与p53表达、由MIB-1表达定义的肿瘤增殖以及雌激素受体状态的相关性。采用免疫组织化学方法检测177例浸润性乳腺癌石蜡包埋组织中Bcl-2、Bax、p53、雌激素受体（ER）和MIB-1的表达。抗凋亡蛋白Bcl-2的表达与促凋亡蛋白Bax无关。Bcl-2免疫染色与组织学分级增加、p53和MIB-1呈负相关（分别为P < 0.0001、P < 0.05和P < 0.0001），与ER免疫染色升高呈正相关（r = 0.305，P < 0.0001）。相反，促凋亡蛋白Bax的表达与组织学分级增加、p53、MIB-1或ER状态无关。Bcl-2表达和Bax表达均与年龄、绝经状态、肿瘤大小、组织学类型或腋窝淋巴结状态无关。这些结果表明，Bcl-2与良好的预后标志物相关，Bax的调节较为复杂，不一定与乳腺癌中的突变p53状态相关。
