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[Cancer Research 62, 4849-4853, September 1, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Expression of Estrogen Receptor (ER) ßcx Protein in ER{alpha}-positive Breast Cancer

Specific Correlation with Progesterone Receptor1

Shigehira Saji2, Yoko Omoto, Chikako Shimizu, Margaret Warner, Yukiko Hayashi, Shin-ichiro Horiguchi, Toru Watanabe, Shin-ichi Hayashi, Jan-Åke Gustafsson and Masakazu Toi

Department of Surgery, Breast Oncology Unit [S. S., M. T.] and Department of Pathology [Y. H., S-i. Ho.], Tokyo Metropolitan Komagome Hospital, 113-8677 Tokyo, Japan; Division of Endocrinology, Saitama Cancer Center Research Institute, 362-0806 Saitama, Japan [Y. O., S-i. Ha.]; Department of Medical Oncology, National Cancer Center Hospital, 104-0045 Tokyo, Japan [C. S., T. W.]; and Department of Medical Nutrition, Karolinska Institute, Huddinge, S141-86 Sweden [M. W., J-Å. G.]

Estrogen receptor (ER) ßcx, a splice variant of ERß, is a dominant repressor of ER{alpha} function. In this study we investigated the possibility that because the progesterone receptor (PR) gene is a downstream target of activated ER{alpha}, in ER{alpha}-positive breast cancers, expression of ERßcx would result in repression of PR. In ER{alpha}-positive MCF-7 cells, stable transfection of an ERßcx expression vector resulted in reduced expression of PR without affecting ER{alpha} expression. In breast cancers, immunohistochemical evaluation of ER{alpha}-positive foci for the expression of PR and ERßcx revealed a significant correlation between a PR-negative phenotype and the presence of ERßcx within the foci. However, when entire lesions were evaluated by Allred scoring in 115 ER{alpha}-positive breast cancer specimens, the presence of two distinct groups of patients could be discerned. One group expressed ERßcx and had very reduced levels of PR expression, as expected. The second group showed both ERßcx and high levels of PR. To evaluate the role of ERßcx in sensitivity to tamoxifen, 18 core needle biopsies, obtained before preoperative treatment with tamoxifen, were investigated. The results show that expression of ERßcx in primary lesions correlated with a poor response to tamoxifen, especially in cancers with a low PR expression in Allred score. This is the first evidence that evaluation of ERßcx along with PR may contribute to a better characterization of ER{alpha}-positive breast cancers.




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