Charpin C, Garcia S, Bouvier C, Devictor B, Andrac L, Lavaut M N, Allasia C
Department of Pathology, Faculté de Médecine Timone, Marseille, France.
Br J Cancer. 1997;76(3):340-6. doi: 10.1038/bjc.1997.388.
Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by immunohistochemical analysis. Immunodetections were assessed using (1) frozen sections, (2) documented commercially available monoclonal antibody (bcl-2/124, Dako), (3) automation of immunoperoxidase technique (Ventana) and (4) quantitative evaluation of results by image analysis (SAMBA) and statistical analysis of quantitative data (BMDP software). Bcl-2 protein expression was correlated with current prognostic indicators and with molecular markers detected by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not related to patients' age, tumour size and type or lymph node status, but an inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An inverse relationship was also observed between Bcl-2 expression and p53 (P < 0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2-positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is strongly detected in low-grade tumours (well-differentiated) with low (MIB1) growth fraction, but is independent of the tumour progression (size, node status, CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved in response to endocrine therapy (associated to ER/PR/pS2 positive immunoreactions) and probably with chemoresistance mechanisms (inverse relationship with P-gp).
通过免疫组织化学分析，对218例人类乳腺癌中的bcl-2基因表达进行了研究。免疫检测采用以下方法进行评估：（1）冰冻切片；（2）已记录的市售单克隆抗体（bcl-2/124，达科公司）；（3）免疫过氧化物酶技术自动化（Ventana）；（4）通过图像分析（SAMBA）对结果进行定量评估，并对定量数据进行统计分析（BMDP软件）。Bcl-2蛋白表达与当前的预后指标以及通过与检测Bcl-2相同程序检测的分子标志物相关。结果表明，Bcl-2表达与患者年龄、肿瘤大小、类型或淋巴结状态无关，但在Bcl-2与肿瘤分级之间观察到负相关关系（P < 0.0001）。在Bcl-2表达与p53（P < 0.0001）、Ki67/MIB1抗原（P = 0.0012）以及P-糖蛋白（P = 0.002）阳性免疫反应之间也观察到负相关关系。相反，抗Bcl-2阳性反应与雌激素受体阳性（P < 0.001）以及雌激素受体/孕激素受体阳性或雌激素受体/孕激素受体/pS2阳性免疫反应显著相关（P ≤ 0.005）。Bcl-2表达与CD31和组织蛋白酶D表达无关。因此，被认为具有抗凋亡作用的Bcl-2蛋白在人类乳腺癌中呈现出矛盾的表达。在低生长分数（MIB1）的低级别肿瘤（高分化）中可强烈检测到Bcl-2，但它与肿瘤进展（大小、淋巴结状态、CD31和组织蛋白酶D）无关。作用于细胞凋亡的Bcl-2与乳腺癌中的p53基因异常有关。Bcl-2蛋白表达也可能参与内分泌治疗反应（与雌激素受体/孕激素受体/pS2阳性免疫反应相关），并且可能与化疗耐药机制有关（与P-糖蛋白呈负相关）。
