迄今为止，还没有生物标志物可以定义对贝伐单抗（BEV）有反应的患者亚群，贝伐单抗是晚期卵巢癌（OC）的有效治疗选择。在 MITO16A/MaNGO OV-2 试验（化疗联合 BEV 一线治疗晚期 OC 的 IV 期研究）的背景下，我们通过新一代测序评估了 202 的 TP53 突变，并通过免疫组织化学 (IHC) 评估了 p53 表达。和 311 例。我们进一步将 TP53 突变的类型、功能和位点以及 IHC 数据与患者的临床病理特征和生存率相关联。功能未知的 TP53 错义突变（命名为未分类）代表了我们人群中的大多数变异（44.4%），并且与单变量中总生存期 (OS) 的显着改善相关（风险比 [HR] = 0.43，95% 置信区间） [CI] = 0.20-0.92，p = .03）和多变量分析（HR = 0.39，95% CI = 0.18-0.86，p = .02）。 TP53 突变分析与 IHC 之间的一致性为 91%。我们观察到，与 p53 野生型患者相比，p53 IHC 过表达患者的 OS HR 为 0.70，但未达到统计学显着性（p = .31，95% CI = 0.36-1.38）。我们的结果表明，未分类的 TP53 突变的存在对于接受前期 BEV 加化疗的 OC 患者具有良好的预后意义。特别是，未分类的错义 TP53 突变表征了具有显着生存优势的患者亚群，而与临床病理特征无关。我们的研究结果值得未来的研究来确认 TP53 突变对 BEV 治疗的 OC 患者的预后影响，并且值得评估其在未来随机临床研究中的潜在预测作用。© 2024 作者。约翰·威利出版的《国际癌症杂志》

To date, there are no biomarkers that define a patient subpopulation responsive to bevacizumab (BEV), an effective treatment option for advanced ovarian carcinoma (OC). In the context of the MITO16A/MaNGO OV-2 trial, a Phase IV study of chemotherapy combined with BEV in first-line treatment of advanced OC, we evaluated TP53 mutations by next-generation sequencing and p53 expression by immunohistochemistry (IHC) on 202 and 311 cases, respectively. We further correlated TP53 mutations in terms of type, function, and site, and IHC data with patients' clinicopathological characteristics and survival. TP53 missense mutations of unknown function (named unclassified) represented the majority of variants in our population (44.4%) and were associated with a significantly improved overall survival (OS) both in univariable (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.20-0.92, p = .03) and multivariable analysis (HR = 0.39, 95% CI = 0.18-0.86, p = .02). Concordance between TP53 mutational analysis and IHC was 91%. We observed an HR of 0.70 for OS in patients with p53 IHC overexpression compared to p53 wild-type, which however did not reach statistical significance (p = .31, 95% CI = 0.36-1.38). Our results indicate that the presence of unclassified TP53 mutations has favorable prognostic significance in patients with OC receiving upfront BEV plus chemotherapy. In particular, unclassified missense TP53 mutations characterize a subpopulation of patients with a significant survival advantage, independently of clinicopathological characteristics. Our findings warrant future investigations to confirm the prognostic impact of TP53 mutations in BEV-treated OC patients and deserve to be assessed for their potential predictive role in future randomized clinical studies.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.