Abstract
BackgroundThere is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC). The aim of this study was to assess the expression of the receptor isoforms ER-α/-β and PR-A/-B in OC tissue and to analyze its impact on clinical and pathological features and patient outcome.Methods155 OC patients were included who had been diagnosed and treated between 1990 and 2002. Patient characteristics, histology and follow-up data were available. ER-α/-β and PR-A/-B expression were determined by immunohistochemistry.ResultsOC tissue was positive for ER-α/-β in 31.4% and 60.1% and PR-A/-B in 36.2% and 33.8%, respectively. We identified significant differences in ER-β expression related to the histological subtype (p=0.041), stage (p=0.002) and grade (p=0.011) as well as PR-A and tumor stage (p=0.03). Interestingly, median receptor expression for ER-α and PR-A/-B was significantly higher in G1 vs. G2 OC. Kaplan Meier analysis revealed a good prognosis for ER-α positive (p=0.039) and PR-B positive (p<0.001) OC. In contrast, ER-β negative OC had a favorable outcome (p=0.049). Besides tumor grade and stage, Cox-regression analysis showed PR-B to be an independent prognostic marker for patient survival (p=0.009, 95% CI 0.251-0.823, HR 0.455).ConclusionER-α/-β and PR-A/-B are frequently expressed in OC with a certain variability relating to histological subtype, grade and stage. Univariate analysis indicated a favorable outcome for ER-α positive and PR-B positive OC, while multivariate analysis showed PR-B to be the only independent prognostic marker for patient survival. In conclusion, ER and PR receptors may be useful targets for a more individualized OC therapy.
Highlights
There is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC)
Receptor expression in OC tissue OC tissue was positive for ER-α/-β in 31.4% and 60.1% and Progesterone receptor A (PR-A)/-B in 36.2% and 33.8%, respectively (Table 1 and Figure 1A-D)
Univariate Kaplan Meier analysis revealed a good prognosis for ER-α positive (p=0.039) (Figure 3a) and Progesterone receptor B (PR-B) positive OC (p
Summary
There is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC). There are various hypotheses to explain the etiology of ovarian cancer (OC), two of them discussing hormonal influence on OC tumorgenesis [1,2]. The influence of hormones on the development or progression of OC remains under discussion [3,4]. The two steroid hormones estrogen and progesterone act via different hormone receptors. The PR-A isoform for instance lacks only the N-terminal 164 amino acids of isoform PR-B [8,9] Their differential regulation of gene transcription might explain their diverse influence on OC progression and prognosis [10]. The classic steroid hormone receptors ER-α and PR-A show different effects on OC cells in vitro and in vivo than the recently discovered receptors ER-β and PR-B [12,13,14,15,16]
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