Abstract
Ovarian cancer is the main cause of death from gynaecological malignancies. In spite of the efficacy of platinum-paclitaxel treatment in patients with primary epithelial ovarian carcinoma, platinum-based chemotherapy is not curative and resistance remains one of the most important causes of treatment failure. Although ABC transporters have been implicated in cellular resistance to multiple drugs, the clinical relevance of these efflux pumps is still poorly understood. Thus, we examined the prognostic role of transporters of the MRP family (i.e., ABCC1/MRP1, ABCC4/MRP4) to gain insights into their clinical impacts. A case material of 127 patients with ovarian carcinoma at different stages and histotypes was used. The expression of MRP1 and MRP4 was examined by immunohistochemistry using tissue microarrays in tumor specimens collected at the time of initial surgery expression. We found an association between MRP1 expression and grading, and we observed that MRP4 displayed an unfavourable impact on disease relapse in multivariate analysis (HR = 2.05, 95% CI: 1.01–4.11; P = 0.045). These results suggest that in epithelial ovarian cancer, MRP1 may be a marker for aggressiveness because its expression was associated with tumor grade and support that MRP4 may play an unfavourable role in disease outcome.
Highlights
Ovarian cancer is the main cause of death from gynecological malignancies and the majority of epithelial ovarian tumors are diagnosed as advanced stage diseases [1]
We found an association between MRP1 expression and grading, and we observed that MRP4 displayed an unfavourable impact on disease relapse in multivariate analysis (HR = 2.05, 95% CI: 1.01–4.11; P = 0.045)
These results suggest that in epithelial ovarian cancer, MRP1 may be a marker for aggressiveness because its expression was associated with tumor grade and support that MRP4 may play an unfavourable role in disease outcome
Summary
Ovarian cancer is the main cause of death from gynecological malignancies and the majority of epithelial ovarian tumors are diagnosed as advanced stage diseases [1]. Recent studies have shown that ovarian carcinoma is a complex disease that gathers molecularly different tumors sharing the localization more than biological features [2]. The management of ovarian carcinoma includes cytoreductive surgery, followed by platinum (carboplatin or cisplatin) taxane chemotherapy, which has become a standard treatment for advanced stage disease [3, 4]. The limited efficacy of chemotherapy may be dependent on the expression of defence factors which confer increased survival potential for tumor cells and, as a consequence, a multidrug resistant phenotype [5]. An analysis of the expression by tumor cells of members of the ATP Binding Cassette (ABC) efflux transporter superfamily may be useful and could help in the choice of treatments defined on the basis of the molecular features of the tumor
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