The Bcl-2 Protein: a Prognostic Indicator Strongly Related to p53 Protein in Lymph Node-Negative Breast Cancer Patients

作者：Rosella Silvestrini, Silvia Veneroni, Maria Grazia Daidone, Elvira Benini, Patrizia Boracchi, Maura Mezzetti, Giovanni di Fronzo, Franco O. Rilke, Umberto Veronesi · 发表于：JNCI Journal of the National Cancer Institute · 年份：1994 · DOI：10.1093/jnci/86.7.499 · 被引用次数：464 · 研究领域：Cell death mechanisms and regulation、Cancer-related Molecular Pathways、Breast Cancer Treatment Studies

BACKGROUND: 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. PURPOSE: 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. METHODS: 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. RESULTS: 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 surv...