Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting the response to chemotherapy might help select eligible patients and spare non-responding patients from treatment-associated toxicity. Cancer/testis antigens (CTAs) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets for cancer immunotherapies. We analyzed the correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at the protein level and the effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. The correlation between the expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria and platinum sensitivity, measured as platinum-free interval (PFI), progression free (PFS), and overall survival (OS) was explored. The MAGE-A10 protein expression predicted unresponsiveness to platinum-based chemotherapy (p= 0.005), poor platinum sensitivity (p< 0.001), poor PFS (p< 0.001), and OS (p< 0.001). Multivariate analysis identified MAGE-A10 protein expression as an independent predictor of poor platinum sensitivity (p= 0.005) and shorter OS (p< 0.001). Instead, no correlation was observed between the NY-ESO-1 protein expression and response to platinum-based chemotherapy (p= 0.832), platinum sensitivity (p= 0.168), PFS (p= 0.126), and OS (p= 0.335). The MAGE-A10 protein expression reliably identified advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted immunotherapy could represent an important alternative therapeutic option in these cancers.
卵巢癌预后不良。术后标准治疗依赖于铂类化疗，然而相当比例的患者对治疗无反应。识别能够预测化疗反应的标志物可能有助于筛选适合的患者，并使无反应患者免于治疗相关的毒性。癌/睾丸抗原（CTAs）在健康生殖细胞及多种组织来源的恶性细胞中均有表达，这种表达特征使其成为癌症免疫治疗中极具吸引力的靶点。本研究分析了晚期高级别浆液性卵巢癌（HGSOC）患者中MAGE-A10与纽约食管癌-1（NY-ESO-1）CTA蛋白表达水平与铂类化疗疗效的相关性。通过免疫组织化学（IHC）检测了1996年1月至2013年12月期间在本机构接受治疗的93例晚期HGSOC患者福尔马林固定石蜡包埋样本中MAGE-A10与NY-ESO-1蛋白表达情况，并探讨这些标志物表达与铂类化疗反应（依据RECIST 1.1标准评估）、铂类敏感性（以无铂间期、无进展生存期和总生存期衡量）之间的相关性。MAGE-A10蛋白表达可预测对铂类化疗无反应（p=0.005）、铂类敏感性差（p<0.001）、无进展生存期短（p<0.001）及总生存期短（p<0.001）。多变量分析确认MAGE-A10蛋白表达是铂类敏感性差（p=0.005）和总生存期缩短（p<0.001）的独立预测因子。而NY-ESO-1蛋白表达与铂类化疗反应（p=0.832）、铂类敏感性（p=0.168）、无进展生存期（p=0.126）及总生存期（p=0.335）均无显著相关性。MAGE-A10蛋白表达能可靠识别对铂类化疗无反应的晚期HGSOC患者，靶向免疫治疗可能为此类癌症提供重要的替代治疗选择。
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