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

Authors: Dolled-Filhart, M  McCabe, A  Giltnane, J  Cregger, M  Camp, RL  Rimm, DL 
Citation: Dolled-Filhart M, etal., Cancer Res. 2006 May 15;66(10):5487-94.
Pubmed: (View Article at PubMed) PMID:16707478
DOI: Full-text: DOI:10.1158/0008-5472.CAN-06-0100

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.


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CRRD Object Information
CRRD ID: 2289831
Created: 2008-02-13
Species: All species
Last Modified: 2008-02-13
Status: ACTIVE


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