Silvestrini R, Veneroni S, Daidone M G, Benini E, Boracchi P, Mezzetti M, Di Fronzo G, Rilke F, Veronesi U
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
J Natl Cancer Inst. 1994 Apr 6;86(7):499-504. doi: 10.1093/jnci/86.7.499.
The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohistochemical procedures in hormonally regulated epithelia.
We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features.
The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [3H]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [3H]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique.
A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [3H]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [3H]thymidine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [3H]thymidine-labeling index was still statistically significant as a predictor for both events.
The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.
bcl-2基因（也称为BCL2）编码一种线粒体蛋白，被认为可防止正常细胞凋亡。该蛋白已通过免疫组织化学方法在激素调节的上皮细胞中检测到。
我们分析了Bcl-2表达对淋巴结阴性乳腺癌6年无复发生存率和总生存率的预测相关性，这些乳腺癌与病理特征（肿瘤大小）和生物学特征（[3H]胸苷标记指数、p53蛋白表达和雌激素受体[ER]状态）相关。
通过免疫组织化学检测283例仅接受局部区域治疗直至复发的淋巴结阴性可切除乳腺癌石蜡包埋切片中Bcl-2和p53的表达。在用[3H]胸苷孵育新鲜肿瘤组织后，在组织学切片上评估[3H]胸苷标记指数，并通过葡聚糖包被活性炭吸收技术测定ER含量。
与大的、ER阴性、快速增殖且p53阳性的肿瘤相比，在小的、ER阳性、缓慢增殖且p53阴性的肿瘤中观察到Bcl-2阳性细胞的比例显著更高。观察到Bcl-2与p53表达之间的关联比这些变量与[3H]胸苷标记指数之间的关联更强。在单变量分析中，Bcl-2和p53表达、[3H]胸苷标记指数、肿瘤大小和ER状态是无复发生存率的指标，除肿瘤大小外，也是手术后6年内总生存率的指标。在多变量分析中，在存在p53表达的情况下，Bcl-2未能维持其对无复发生存率和总生存率的预后作用，而[3H]胸苷标记指数作为这两个事件的预测指标仍具有统计学意义。
Bcl-2表达对6年无复发生存率和总生存率的预测作用主要取决于p53表达。
