Abstract
Expression of the progesterone receptor (PR) has been reported to influence survival outcomes in patients with ovarian high-grade serous carcinoma (HGSC). In the present study, we attempted to investigate the association among PR and its isoforms' expression, platinum sensitivity, and survival in ovarian HGSC. This retrospective study reviewed ovarian HGSC patients who received surgery followed by adjuvant chemotherapy. We analyzed total PR and PR isoform-B (PR-B) expression by immunohistochemical staining and quantified using the H-score. Then, we compared platinum sensitivity and survival outcomes between those patients with weak and strong PR-B expression. Cisplatin viability assays were carried out in ovarian HGSC cell lines (OC-3-VGH and OVCAR-3) with different PR-B expression. Among 90 patients, 49 and 41 patients were considered to have platinum-sensitive and platinum-resistant disease, respectively. Pearson's correlation model showed that the H-score of total PR correlated positively with PR-B (r = 0.813). The PR-B H-score of tumors was significantly higher in the platinum-sensitive group (p = 0.004). Multivariate analysis revealed that the PR-B H-score and optimal debulking status were independent factors predicting platinum sensitivity. When compared with strong PR-B expression, patients with weak PR-B had significantly poorer progression-free (p = 0.021) and cancer-specific survival (p = 0.046). In a cell model, cisplatin-resistant OC-3-VGH cells expressed a lower level of PR-B than wild-type cells. Overexpression of PR-B or progesterone could increase cisplatin sensitivity in both OC-3-VGH and OVCAR-3 cells via the mechanism of promoting cisplatin-related apoptosis. When compared to weak PR-B, ovarian HGSC patients with a strong PR-B expression had a better chance of platinum sensitivity and survival, and this finding was compatible with our experimental results. Progesterone seemed to be a platinum sensitizer, but the value of adding progesterone in the treatment of ovarian HGSC should be further investigated.
Highlights
The standard treatment for advanced-stage epithelial ovarian cancer (EOC) is primary debulking surgery followed by adjuvant chemotherapy
According to the receiver operating characteristic (ROC) curve analysis, we found that the optimal cut-off value of progesterone receptor (PR)-B Hscore to predict platinum-sensitivity was 12.5 (AUC 0.664, 95% confidence interval (CI): 0.552–0.776)
In our study by adding P4, we found both ovarian cancer cells with weak and strong PR isoform-B (PR-B) became more sensitive to cisplatin treatment
Summary
The standard treatment for advanced-stage epithelial ovarian cancer (EOC) is primary debulking surgery followed by adjuvant chemotherapy. A recent meta-analysis has shown that strong PR expression was independently associated with improved disease-specific survival in patients with ovarian cancer [11]. We attempted to investigate the association among PR and its isoforms’ expression, platinum sensitivity, and survival in ovarian HGSC. We compared platinum sensitivity and survival outcomes between those patients with weak and strong PR-B expression. When compared with strong PR-B expression, patients with weak PR-B had significantly poorer progression-free (p = 0.021) and cancer-specific survival (p = 0.046). Conclusions: When compared to weak PR-B, ovarian HGSC patients with a strong PR-B expression had a better chance of platinum sensitivity and survival, and this finding was compatible with our experimental results. Progesterone seemed to be a platinum sensitizer, but the value of adding progesterone in the treatment of ovarian HGSC should be further investigated
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