Currently, there are limited and conflicting reports on the prognostic utility of PIK3CA and associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CA copy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations-the majority (n=37, 77.1%) PIK3CA mutations. PIK3CA mutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P=0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P=0.004]. On multivariable analysis, PIK3CA status was not associated with overall survival (P=0.103) or progression-free survival (P=0.240) at 5 yrs, nor was PIK3CA copy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17-0.89; P=0.025)] but not overall survival (P=0.087). The correlation of PIK3CA with pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CA assessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.

中文翻译：

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初次手术治疗的宫颈癌患者中 PIK3CA 突变、CNV 状态和磷酸化 AKT 表达的患病率和预后意义。

目前，关于 PIK3CA 和相关通路标志物对初次手术治疗宫颈癌的预后效用的报道有限且相互矛盾。此外，目前的研究缺乏放疗和/或化疗辅助治疗的完整特征。我们的目的是记录初次手术治疗的宫颈癌患者中 PI3K/AKT 通路突变、拷贝数变异和磷酸化 AKT 状态的患病率、临床病理学、辅助治疗细节和预后价值。对 185 名宫颈癌患者进行了回顾性队列研究，这些患者均在同一家三级机构接受了初次手术。使用下一代测序和数字 PCR 分别确定 PI3K/AKT 通路突变状态和 PIK3CA 拷贝数变异，并使用荧光免疫组织化学测量磷酸化 AKT 表达。总共 185 个肿瘤中的 179 个 (96.8%) 被成功测序；48 名 (26.8%) 的 PI3K/AKT 通路突变呈阳性——大多数 (n=37, 77.1%) PIK3CA 突变。PIK3CA 突变与病理阳性淋巴结相关 [12 个 (32%) vs. 22 个 (16%)；P=0.022]和术后放化疗的指征[17（45.9%）vs. 32（22.5%）；P=0.004]。在多变量分析中，PIK3CA 状态与 5 年总生存期 (P=0.103) 或无进展生存期 (P=0.240) 无关，PIK3CA 拷贝数变异状态也与此无关。磷酸化 AKT ≤ 中位数可显着预测无进展生存期 [多变量风险比 0.39 (0.17-0.89；P=0.025)]，但不能显着预测总生存期 (P=0.087)。PIK3CA 与病理阳性淋巴结状态相关，但与生存结果缺乏相关性，可能是由于术后辅助治疗的使用。根治性子宫切除术前的 PIK3CA 评估可能有助于识别淋巴结阳性疾病风险较高的患者。