Progesterone receptor isoforms, PR-B and PR-A in breast cancer: Correlations with clinicopathologic tumor parameters and expression of AP-1 factors

In the present study, we used Western blot analysis to determine the expres sion of the progesterone receptor (PR) isoforms, PR-B and PR-A, in breast t umors (n = 53), and correlated the expression patterns of the two isoforms with the clinicopathological parameters of these tumors and with expression of the AP-1 family of transcription factors. Expression of the two PR isof orms correlated significantly with each other, indicating that the expressi on of the two isoforms is probably regulated in a correlated fashion. Expre ssion of both isoforms correlated significantly with expression of the estr ogen receptor (ER). Furthermore, expression of PR-B was found to correlate significantly with the absence of ErbB2/neu. For the AP-1 factors, Fra-1 ex pression showed an inverse correlation with PR-B expression. In contrast, e xpression of FosB correlated significantly with expression of both isoforms , and the association was stronger with PR-B expression. An analysis of the ratio of expression of the two isoforms showed that most of the tumors exp ressed PR-A levels which were equal or higher than the corresponding PR-B e xpression levels (together 94% of the analyzed tumors) indicating that, in mammary carcinomas, a predominance of the PR-A isoform over the PR-B isofor m seems to be the case. While there was no statistically significant correl ation with age, staging and histological type, expression of both isoforms correlated with a more differentiated phenotype (G1/G2 grading). However, t h is association was stronger for PR-B. Also, a PR-A less than or equal to PR-B expression level was associated with G1/G2 grading, while a PR-A > PR- B expression level showed an association with a more undifferentiated pheno type (G3 grading). The expression level of the two PR isoforms might prove to be of prognostic and/or predictive value, especially since the two isofo rms have been shown to be functionally different and to modulate the respon se of tumor cells to progestins and antiprogestins differently. Copyright ( C) 2001 S. Karger AG, Basel.