Drastic decrease of progesterone receptor form B but not A mRNA reflects poor patient prognosis in endometrial cancers

Abstract

Objectives. Progesterone receptor (PR) has been recognized as an important factor that correlates with success of endocrine treatment and patients' prognoses in endometrial cancers (EC). This study was designed to determine the clinical implications of expression of PR form A (PR-A) and B (PR-B) in EC. Methods. We have quantified the mRNA levels of total PR (PR-AB) and PR-B by real-time RT-PCR in 120 EC and 40 normal endometria (NE). We then analyzed the correlation between expression levels of each receptor and clinical characteristics including clinical stages, histological grades, depth of myometrial invasion and patients' prognoses. Results. Although the expression level of PR-B is correlated with that of PR-A, the expression pattern of PR-B classified according to clinical characteristics was different from that of PR-A. We found that high PR-B mRNA levels but not PR-A mRNA levels correlated significantly with survival, independent of clinical characteristics including clinical stages, histological grades and depth of myometrial invasion. Percentage of PR-B to total PR (B/AB) in EC is widely distributed and the ratios of middle B/AB group (0.15 < B/AB < 0.35) are 75% in NE, 47% in surviving cases of EC and 18% in dead cases of EC at 5 years, respectively. Conclusions. These results taken together indicate that PR-B may have a different function from PR-A and the intact coordinate expression of PR isoforms was disrupted in EC, especially in poor prognostic case. The measurement of PR isoforms has prognostic value in EC.