bcl-2 and apoptosis in lymph node positive breast carcinoma

Cancer. 1998 Apr 1;82(7):1296-302.

Abstract

Background: Because bcl-2 can block apoptosis in vitro, and because lower levels of apoptosis might lead to malignant cell accumulation and therefore to a more aggressive clinical course, the authors tested the hypothesis that high bcl-2 and low apoptosis would result in a worse prognosis for breast carcinoma patients.

Methods: Primary breast tumor specimens from 979 patients with positive axillary lymph nodes were evaluated for bcl-2 protein expression by immunohistochemistry (IHC). Apoptosis was evaluated by using IHC to detect 3' DNA fragments end-labeled with biotinylated uridine. Results were analyzed with respect to patient characteristics, prognostic factors, and clinical outcome. Median follow-up was 61 months.

Results: High bcl-2 expression was significantly associated with a number of favorable prognostic factors, including a lower number of positive lymph nodes, absence of p53 protein accumulation, estrogen receptor (ER) and progesterone receptor (PR) positivity, diploidy, and a lower proliferative rate. However, although bcl-2 is generally considered a negative regulator of apoptosis, in these tumors there was no significant association between bcl-2 and apoptosis. Patients with high bcl-2 expression had significantly improved disease free survival (DFS) (P < 0.0001) and overall survival (OS) (P < 0.0001). In a multivariate analysis, bcl-2 expression was independently associated with better DFS (P = 0.004). Regarding apoptosis, the presence of > or = 1% apoptotic cells was significantly associated with a greater number of positive lymph nodes, p53 protein expression, ER and PR negativity, aneuploidy, and a higher proliferation rate, although there was no significant association with a worse clinical outcome when this dichotomized cutoff was used.

Conclusions: For lymph node positive breast carcinoma patients, high bcl-2 expression is associated with a number of good prognostic factors and is independently associated with better clinical outcome. Apoptosis is associated with a number of poor prognostic factors but not with a significantly worse outcome.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Division
  • Disease-Free Survival
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis / diagnosis*
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Survival Rate

Substances

  • Proto-Oncogene Proteins c-bcl-2