title: Progesterone receptor isoforms, PR-B and PR-A, in breast cancer: correlations with clinicopathologic tumor parameters and expression of AP-1 factors.
abstract: 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.
authors.affiliation: Institute of Pathology, Department of Gynecopathology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Bamberger
authors.forename: K
authors.initials: K
authors.lastname: Milde-Langosch
authors.forename: H M
authors.initials: HM
authors.lastname: Schulte
authors.forename: T
authors.initials: T
authors.lastname: Löning
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D018567:Breast Neoplasms, Male / Q000737:chemistry / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000032:analysis; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis*; D014407:Tumor Cells, Cultured; D000099169:Fos-Related Antigen 1
chemical_list: D020033:Protein Isoforms; D016760:Proto-Oncogene Proteins c-fos; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000099169:Fos-Related Antigen 1; C101118:progesterone receptor A; C097314:progesterone receptor B