Goodell Vivian, Salazar Lupe G, Urban Nicole, Drescher Charles W, Gray Heidi, Swensen Ron E, McIntosh Martin W, Disis Mary L
Center for Translational Medicine in Women's Health, Tumor Vaccine Group, University of Washington, and the Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
J Clin Oncol. 2006 Feb 10;24(5):762-8. doi: 10.1200/JCO.2005.03.2813. Epub 2006 Jan 3.
Presence of intratumoral T-cell infiltration has been linked to improved survival in ovarian cancer patients. We questioned whether antibody immunity specific for ovarian cancer tumor antigens would predict disease outcome. We evaluated humoral immune responses against ovarian cancer antigens p53, HER-2/neu, and topoisomerase IIalpha.
Serum was collected from 104 women (median age, 59 years; range, 34 to 89 years) at the time of their initial definitive surgery for ovarian cancer. Serum was analyzed by enzyme-linked immunosorbent assay for antibodies to p53, HER-2/neu, and topoisomerase IIalpha proteins. Antibody immunity to tetanus toxoid was assessed as a control. The incidence of humoral immunity at the time of diagnosis to any of these three antigens was tabulated. For patients with advanced-stage disease (III/IV), correlation was made between the presence of tumor-specific immunity at the time of diagnosis and overall survival. Patients were followed for a median of 1.8 years.
Multivariate analysis showed the presence of p53 antibodies to be an independent variable for prediction of overall survival in advanced-stage patients. Overall survival was significantly higher for patients with antibodies to p53 when compared with patients without p53 antibodies (P = .01). The median survival for p53 antibody-positive patients was 51 months (95% CI, 23.5 to 60.5 months) compared with 24 months (95% CI, 19.4 to 28.6 months) for patients without antibodies to p53.
Data presented here demonstrate that advanced stage ovarian cancer patients can have detectable tumor-specific antibody immunity and that immunity to p53 may predict improved overall survival in patients with advanced-stage disease.
肿瘤内T细胞浸润与卵巢癌患者生存率提高有关。我们探讨针对卵巢癌肿瘤抗原的抗体免疫是否能预测疾病转归。我们评估了针对卵巢癌抗原p53、HER-2/neu和拓扑异构酶IIα的体液免疫反应。
收集104例女性(中位年龄59岁;范围34至89岁)初次接受卵巢癌根治性手术时的血清。采用酶联免疫吸附测定法分析血清中针对p53、HER-2/neu和拓扑异构酶IIα蛋白的抗体。评估破伤风类毒素抗体免疫作为对照。将诊断时对这三种抗原中任何一种的体液免疫发生率制成表格。对于晚期疾病(III/IV期)患者,分析诊断时肿瘤特异性免疫的存在与总生存期之间的相关性。对患者进行了中位时间为1.8年的随访。
多变量分析显示,p53抗体的存在是晚期患者总生存期预测的独立变量。与无p53抗体的患者相比,有p53抗体的患者总生存期显著更长(P = 0.01)。p53抗体阳性患者的中位生存期为51个月(95% CI,23.5至60.5个月),而无p53抗体的患者为24个月(95% CI,19.4至28.6个月)。
本文数据表明,晚期卵巢癌患者可检测到肿瘤特异性抗体免疫,且对p53的免疫可能预测晚期疾病患者总生存期的改善。