Prevalence and Prognostic Significance of PIK3CA Mutation and CNV Status and Phosphorylated AKT Expression in Patients With Cervical Cancer Treated With Primary Surgery.

IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY
Kevin Martell, John B McIntyre, Tasnima Abedin, Elizabeth N Kornaga, Angela M Y Chan, Emeka Enwere, Martin Köbel, Michelle L Dean, Tien Phan, Prafull Ghatage, Susan P Lees-Miller, Corinne M Doll
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引用次数: 0

Abstract

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.

宫颈癌初治手术患者中 PIK3CA 突变和 CNV 状态以及磷酸化 AKT 表达的发生率和预后意义
目前,关于 PIK3CA 和相关通路标记物对初治手术治疗的宫颈癌的预后作用的报道有限且相互矛盾。此外,目前的研究还缺乏对 RT 和/或化疗辅助治疗的完整描述。我们旨在记录宫颈癌初治手术患者中 PI3K/AKT 通路突变、拷贝数变异和磷酸化 AKT 状态的发生率、临床病理、辅助治疗细节和预后价值。我们对在一家三级医疗机构接受初次手术治疗的 185 例宫颈癌患者进行了临床病理学回顾。下一代测序和数字 PCR 分别用于确定 PI3K/AKT 通路突变状态和 PIK3CA 拷贝数变异,荧光免疫组化则用于测量磷酸化 AKT 的表达。185例肿瘤中有179例(96.8%)成功测序;48例(26.8%)PI3K/AKT通路突变阳性,其中大多数(37例,77.1%)为PIK3CA突变。PIK3CA突变与病理淋巴结阳性[12(32%)vs 22(16%);P =0.022]和术后化放疗指征[17(45.9%)vs 32(22.5%);P =0.004]有关。在多变量分析中,PIK3CA状态与5年的总生存期(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无进展生存期无关。磷酸化AKT≤中位数可显著预测无进展生存期[多变量危险比0.39 (0.17-0.89; P =0.025)],但与总生存期无关(P =0.087)。PIK3CA与病理淋巴结阳性状态相关,但与生存结果无关,这可能与术后辅助治疗的使用有关。在根治性子宫切除术前对PIK3CA进行评估可能有助于识别出结节阳性疾病风险较高的患者。
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来源期刊
CiteScore
3.90
自引率
12.50%
发文量
154
审稿时长
6-12 weeks
期刊介绍: International Journal of Gynecological Pathology is the official journal of the International Society of Gynecological Pathologists (ISGyP), and provides complete and timely coverage of advances in the understanding and management of gynecological disease. Emphasis is placed on investigations in the field of anatomic pathology. Articles devoted to experimental or animal pathology clearly relevant to an understanding of human disease are published, as are pathological and clinicopathological studies and individual case reports that offer new insights.
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