Mignogna Chiara, Staropoli Nicoletta, Botta Cirino, De Marco Carmela, Rizzuto Antonia, Morelli Michele, Di Cello Annalisa, Franco Renato, Camastra Caterina, Presta Ivan, Malara Natalia, Salvino Angela, Tassone Pierfrancesco, Tagliaferri Pierosandro, Barni Tullio, Donato Giuseppe, Di Vito Anna
Department of Health Science, Pathology Unit, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy.
Department of Experimental and Clinical Medicine, Medical Oncology, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy.
J Ovarian Res. 2016 May 21;9(1):31. doi: 10.1186/s13048-016-0238-7.
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.
高级别浆液性卵巢癌(HGSOC)是上皮性卵巢癌(EOC)的主要组织学类型,其特征为诊断时处于晚期、TP53频繁突变、进展迅速以及对铂类化疗高度敏感。迄今为止,晚期EOC的标准一线化疗包括铂盐和紫杉醇,可联合或不联合贝伐单抗。主要的预后因素是铂类治疗结束后的反应持续时间(无铂间期),约10%-20%的EOC患者患有铂类难治性疾病或出现早期耐药(无铂间期短于6个月)。基于这些情况,建议仔细选择能够从化疗中获益的患者,以避免不必要的副作用并获得更好的疾病转归。在这项回顾性研究中,根据铂类状态对41例HGSOC病例进行了极光激酶A(AURKA)的免疫组化评估。考虑到AURKA阳性细胞的数量和强度,我们构建了一个预测评分,能够高精度地区分铂敏感患者和铂耐药患者(p<0.001)。此外,我们观察到AURKA过表达与较差的总生存期相关(p=0.001;HR 0.14)。我们在此建议将AURKA作为预测HGSOC生物学行为的新的有效工具。特别是,我们的结果表明AURKA既是铂耐药的预测指标,也是预后因素,值得在前瞻性临床试验中进一步研究。事实上,在个性化医疗时代,AURKA可以帮助临床医生选择最佳治疗方案,同时也代表了EOC治疗中一个有前景的新治疗靶点。