A shift from nuclear to cytoplasmic breast cancer metastasis suppressor 1 expression is associated with highly proliferative estrogen receptor-negative breast cancers

Tumour Biol. 2009;30(3):148-59. doi: 10.1159/000228908. Epub 2009 Jul 16.

Abstract

Background/aims: To determine breast cancer metastasis suppressor 1 (BRMS1) expression in breast cancers and the efficacy of BRMS1 as a prognostic indicator, BRMS1 expression was assessed in two sets of breast cancer tissues.

Methods: Epithelial cells from 36 frozen samples of breast cancers and corresponding normal breast were collected by laser capture microdissection and assessed for BRMS1 by quantitative RT-PCR and immunohistochemistry. BRMS1 was also evaluated by immunohistochemistry in a tissue microarray of 209 breast cancers and correlated with indicators of prognosis [estrogen receptor (ER), progesterone receptor (PR), ErbB2, p53, p27(Kip1), Bcl2 and Ki-67].

Results: BRMS1 mRNA and protein were higher in 94 and 81%, respectively, of breast cancers than in corresponding normal epithelium. BRMS1 localization was predominantly nuclear, but 60-70% of cancers also exhibited cytoplasmic immunostaining. Breast cancers with lower nuclear than cytoplasmic BRMS1 (nuclear score - cytoplasmic score < or =0; 11% of cancers) had lower ER, lower PR and higher Ki-67 expression. There was also a trend toward poorer overall survival in this group of cancers, but this was only of borderline significance (p = 0.073). In Cox proportional hazards models, loss of nuclear BRMS1 was not a significant predictor of overall survival.

Conclusions: Loss of nuclear BRMS1 was associated with ER-negative cancers and a high rate of proliferation, but was not an independent indicator of prognosis.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Nucleus / metabolism*
  • Cell Proliferation
  • Cytoplasm / metabolism*
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lasers
  • Microdissection
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Staging
  • Prognosis
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics
  • Repressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Array Analysis

Substances

  • BRMS1 protein, human
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Repressor Proteins