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Endocrinology |
Departments of Medicine [S. A. W. F., R. S., I. P., C. K. O., G. M. C.] and Pathology [S. K. M., D. C. A.], Breast Center, Baylor College of Medicine, Houston, Texas 77030, and Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709-3398 [J. T. M.]
The recent discovery of a second estrogen receptor (ER), designated ERß, raises pressing questions about its role in estrogen regulation of human breast cancer cells and its significance for the prediction of recurrence and treatment responses in clinical breast cancer. Most of what we know about ERß expression comes from studies examining a limited number of samples at the RNA level. We have now generated a monoclonal antibody useful for the detection of ERß at the protein level in archival, formalin-fixed breast tumors and have examined its expression using immunohistochemistry in a pilot series of 242 breast cancer patients. Coexpression of ERß and ER
was found in the majority of the tumors, with 76% of the tumors expressing ERß as determined by immunohistochemistry. ER, but not ERß, was strongly associated with progesterone receptor expression, suggesting that ER is the predominant regulator of this estrogen-induced gene in breast tumors. Although ER expression was positively correlated with low tumor grade, diploidy, and low S-phase fraction, all biological parameters of a good prognostic profile, ERß trended toward an association only with aneuploidy; no association with tumor grade or S-phase fraction was seen for ERß. We found that ERß expression does cause false positive readings for ER. These results suggest that ERß expression is not a surrogate for ER in clinical breast tumors and, as such, could be a useful biomarker in its own right.
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