Abstract P6-05-13: Tumor and cellular distribution of activated forms of ER and PR in breast cancers

Abstract

Abstract Background: Hormonal therapy is considered one of the most effective treatment options for patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancers (BC); however only a 50% objective response rate is observed as 1st line therapy of ER positive (ERpos) tumors (Bonneterre, 2001). An IHC diagnostic test to identify the activated form of the ER and PR has previous been described (ASCO 2013 abst # 592, 593 & 5602). The nuclear morphological of distribution of the ER and PR can be categorized in two patterns, a presumably not-activated D (diffuse pattern) or activated A (aggregated pattern). This classification is correlated with antiestrogen treatment outcome (ASCO 2013, abst # 592), and correlated with antiprogestin activity in vitro (AACR 2013, abst # 1317). Clinical activity of antiprogestins has been previously described (Robertson 1999, Jonat 2002). It is generally accepted that expression of PR is under the transcriptional control of ER, thus targeting ER can potentially suppresses PR expression. However, in breast cancer tissues although both ER and PR are present in the tumor specimen, there is low level of co-expression of ER/PR at the cellular level (ASCO 2013, abstract # 596). The goal of the study is to elucidate whether or not the activated form of ER and PR were coexpressed. Method: 293 ERpos or PRpos BC were obtained from the Oscar-Lambret Cancer Center, Lille, France. Each sample was analyzed with specific antibodies for ERα, PR A or PR B; a subset (53 for PR A and 49 for PR B cases) was analyzed by immunochemical duel staining on the same paraffin tumor section for ERα and PR A or PR B. Tumors were deemed receptor positive if >10% of the tumors cells (tc) were stained. Samples processed for duel staining came from the same dataset and were selected if they had both ERα and PR A and/or PR B present in more than 10% and less than 80% of stained tc. The distribution of ERα, PR A, PR B tc was described. Determination of the activated form of ERα (AERpos) and PR A (APRpos A), PR B (APRpos B) was performed using the previously described IHC technique at 100X magnification. Results: Standard receptor positivity (% of tumors tested) was as follows; ERα 85%, PR A 61% and PR B 65%, either PR A or B 68%. Duel staining receptor positivity (% of tumors) showed for the PR A subset: 72% ER pos, 74% PR A pos, and 9% ER/PR (% of tumors co-expressing); for the PR B subset: ER 60%, PR B 100%, and 13% ER/PR (% of co-expressing); Subnuclear Morphology: 216 cases were ER and PR positive, and of these, 23% were AERpos, 23% were APRpos A, 24%, APRpos B% and 31% APRpos for either A or B. In the 216 case dataset, 18% of the tumors had both AER and APR A or APR B; However, using the duel staining method no cases had more than 10% of the tc co-expressing i.e. AERpos and APRpos, indicating that the co-expression was principally at the tumor level and not at the cellular level. Conclusion: As known, BC commonly express both ER and PR; however the co-expression of ER and PR in malignant cells is uncommon, and this co-expression of ER and PR could be explained by chance. Although AER and APR are expressed within the same tumor, the activated forms of the ER and PR are not co-expressed at the cellular level. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-13.