Prognostic significance of Bcl-2 in invasive mammary carcinomas: a comparative clinicopathologic study between "triple-negative" and non-"triple-negative" tumors

Hum Pathol. 2012 Jan;43(1):23-30. doi: 10.1016/j.humpath.2011.04.011. Epub 2011 Jul 20.

Abstract

Bcl-2 is a tumorigenic protein that is expressed in 25% to 50% of breast cancers. Although its expression has been widely accepted as a favorable prognostic marker, its protective mechanism of action remains unclear. "Triple-negative" tumors are an aggressive subgroup known to carry a poor prognosis. Studies documenting prognostic significance of Bcl-2 expression in triple-negative in comparison to non-triple-negative breast cancers are limited. Bcl-2 expression was correlated with tumor size, grade, histologic type, lymphovascular invasion, lymph node status, patients' overall survival, estrogen receptor, progesterone receptor, Her-2, p53, and epidermal growth factor receptor in 124 triple-negative and 458 non-triple-negative tumors. There were significant differences between triple-negative and non-triple-negative tumors in their relationship to Bcl-2 expression (81% versus 29%, respectively) and tumor aggression. As previously reported, in non-triple-negative tumors, Bcl-2 positivity correlated with less aggressive tumors (94% of grade I tumors were Bcl-2+ versus 62% of grade III tumors, P < .011) and overall survival (P = .008). However, the opposite was true in patients with triple-negative tumors, where Bcl-2 positivity was associated with poorer survival (P = .64). In triple-negative tumors, Bcl-2 positivity was not associated with any of the aforementioned parameters except for a lower incidence of lymph node metastasis. Moreover, by Cox regression analysis of all variables, in patients with triple-negative tumors, lymphovascular invasion (P = .009) and Bcl-2 expression (P = .028) were predictors of poor survival. In conclusion, there are major clinicopathologic differences between breast cancer phenotypes. Our results establish the value of using Bcl-2 in prognostic stratification of patients and its potential therapeutic implications in selecting patients for treatment.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / secondary
  • Female
  • Humans
  • Lymphatic Metastasis
  • Mastectomy
  • Microarray Analysis
  • Middle Aged
  • Neoplasms, Multiple Primary
  • Phenotype
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2