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 expression of the progesterone receptor (PR) isoforms, PR-B and PR-A, in breast tumors (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 isoforms correlated significantly with each other, indicating that the expression of the two isoforms is probably regulated in a correlated fashion. Expression of both isoforms correlated significantly with expression of the estrogen 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 expression showed an inverse correlation with PR-B expression. In contrast, expression 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 expressed PR-A levels which were equal or higher than the corresponding PR-B expression levels (together 94% of the analyzed tumors) indicating that, in mammary carcinomas, a predominance of the PR-A isoform over the PR-B isoform seems to be the case. While there was no statistically significant correlation with age, staging and histological type, expression of both isoforms correlated with a more differentiated phenotype (G1/G2 grading). However, this association was stronger for PR-B. Also, a PR-A < or = 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 phenotype (G3 grading). The expression level of the two PR isoforms might prove to be of prognostic and/or predictive value, especially since the two isoforms have been shown to be functionally different and to modulate the response of tumor cells to progestins and antiprogestins differently. Copyright 2001 S. Karger AG, Basel