Quantitative in situ analysis of beta-catenin expression in breast cancer shows decreased expression is associated with poor outcome

Cancer Res. 2006 May 15;66(10):5487-94. doi: 10.1158/0008-5472.CAN-06-0100.

Abstract

The role of beta-catenin in breast cancer and its prognostic value is controversial. The prognostic value had been assessed previously in a series of nonquantitative immunohistochemical studies with conflicting results. In efforts to clarify the relationship between beta-catenin protein expression and breast cancer prognosis, we have assessed a retrospective 600 case cohort of breast cancer tumors from the Yale Pathology archives on tissue microarrays. They were assessed using automated quantitative analysis (AQUA) with a series of array-embedded cell lines for which the beta-catenin concentration was standardized by an ELISA assay. The expression levels of the standard clinical markers HER2, estrogen receptor (ER), progesterone receptor (PR), and Ki-67 were also assessed on the same cohort. X-tile software was used to select optimal protein concentration cutpoints and to evaluate the outcome using a training set and a validation set. We found that low-level expression of membranous beta-catenin is associated with significantly worse outcome (38% versus 76%, 10-year survival, validation set log-rank P = 0.0016). Multivariate analysis of this marker, assessed in a proportional hazards model with tumor size, age, node status, nuclear grade, ER, PR, HER2, and Ki-67, is still highly significant with a hazard ratio of 6.8 (P < 0.0001, 95% confidence interval, 3.1-15.1). These results suggest that loss of beta-catenin expression at the membrane, as assessed by objective quantitative analysis methods, may be useful as a prognostic marker or may be part of a useful algorithm for prognosis in breast cancer.

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

  • Algorithms
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / biosynthesis*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Data Interpretation, Statistical
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Microarray Analysis / methods
  • Middle Aged
  • Prognosis
  • beta Catenin / analysis
  • beta Catenin / biosynthesis*

Substances

  • Biomarkers, Tumor
  • beta Catenin