Quantitative in situ analysis of beta-catenin expression in breast cancer shows decreased expression is associated with poor outcome.
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.
Dolled-Filhart
Marisa
M
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
McCabe
Anthony
A
Giltnane
Jennifer
J
Cregger
Melissa
M
Camp
Robert L
RL
Rimm
David L
DL
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D003627:Data Interpretation, Statistical; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D011379:Prognosis; D051176:beta Catenin / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D051176:beta Catenin