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Abstract
High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10–0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-016-0238-7) contains supplementary material, which is available to authorized users.
Highlights
Epithelial ovarian cancer (EOC) represents the 5th leading cause of cancer-related death worldwide [1] with approximately 225.500 new diagnoses per year and a mortality rate greater than 30 % [2]
We investigated the association between the expression of Aurora Kinase A (AURKA) in High-Grade Serous Ovarian Carcinoma (HGSOC) patients’ specimens and clinical outcome, taking into account both response to chemotherapy and survival
To verify the reliability of the sample, we evaluated if patients with a platinum-sensitive disease experienced the longest survival
Summary
Epithelial ovarian cancer (EOC) represents the 5th leading cause of cancer-related death worldwide [1] with approximately 225.500 new diagnoses per year and a mortality rate greater than 30 % [2]. Even though 70–80 % of patients show an initial response to chemotherapy, approximately 25 % relapse within 6 months [8, 9]. According to time to relapse after last chemotherapy administration, EOC patients are classified into three platinum-status groups. Patients who relapse within 6 months are classified as platinum-resistant (PR), and are candidate to alternative treatment schedules that do not include platinum-derived compounds [11, 12]. The platinum-refractory group involves patients who experience disease progression during the course of treatment. This is the subgroup with the worse prognosis and includes less than 10 % of HGSOC patients [14]
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