Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases

Cancer J Sci Am. Jul-Aug 1997;3(4):230-7.

Abstract

Purpose: Dysregulation of genes that control apoptosis can contribute to tumor progression and increased drug resistance. The BCL2 gene and its family member BCL-x as well as the TP53 genes regulate apoptosis and have been shown to have a direct effect on the sensitivity of cancer cells to radiation and chemotherapeutic agents.

Methods: The expression of BCL-x, a BCL2-related protein that is a potent inhibitor of apoptosis, was investigated by immunohistochemical and immunoblot methods in 43 primary untreated breast carcinomas, in conjunction with BCL2 and TP53.

Results: BCL-x protein was overexpressed in 18 of 42 (43%) invasive breast cancers when compared with adjacent normal breast epithelium. Western blot analysis of eight primary breast cancers and five breast cancer cell lines indicated that BCL-xL was the predominant BCL-x protein expressed. Overexpression of BCL-x protein in these tumors was associated with higher tumor grade and increased number of positive nodes. In contrast, BCL2 protein was overexpressed in 19 of 42 tumors (45%) and was strongly correlated with estrogen receptor positivity, lower tumor grade, smaller tumor size, and lower stage. TP53 protein immunostaining was detected in 12 of 40 tumors (29%) and was inversely correlated with BCL2 expression and ER positivity. There was no correlation between the level of BCL-x protein expression and age, tumor size, ER status, and TP53 status. At a median follow-up time of 216 weeks, there was a trend toward decreased overall survival in patients with tumors overexpressing BCL-x.

Conclusions: These findings suggest that expression of BCL-x protein is increased in a significant fraction of invasive breast cancers. In contrast to BCL2 expression, up-regulation of BCL-x protein may be a marker of tumor progression. Additional data including larger numbers of patients, more uniform treatments, and longer follow-up are needed to define the prognostic significance of overexpression of BCL-x during breast cancer progression.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / physiology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / secondary
  • Female
  • Genes, bcl-2
  • Genes, p53
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Staging
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Tumor Cells, Cultured
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein