Abstract
The aim of this study was to evaluate the clinicopathological and prognostic relevance of PIK3CA mutations in Chinese patients with surgically resected cervical cancer. PIK3CA mutations were screened in 771 cervical cancer specimens using reverse transcription polymerase chain reaction and Sanger sequencing. In total, 13.6% (105 of 771) of patients harbored non-synonymous PIK3CA mutations. Patients harboring PIK3CA mutations were older than patients with wild-type PIK3CA (mean age: 50.7 years vs. 47.0 years, P < 0.01). PIK3CA mutations were more commonly observed in postmenopausal patients than in premenopausal patients (19.6% vs. 10.2%, P < 0.01). PIK3CA mutations were more common in squamous cell carcinomas than in non-squamous cell tumors (15.3% vs 7.3%, of P < 0.01). The 3-year relapse-free survival was 90.2% for PIK3CA mutant patients and 80.9% for PIK3CA wild-type patients (P = 0.03). PIK3CA mutation was confirmed as an independent predictor for better treatment outcome in the multivariate analyses (HR = 0.54, 95% CI: 0.29–0.99, P = 0.048). PIK3CA mutations were significantly associated with less distant metastases (mutant-type: 8/105, wild-type: 98/666, p = 0.048). Thus, patients with mutant PIK3CA had distinct characteristics in age, menopausal status, and histological subtype and have better treatment outcome and less distant metastasis after surgery-based multimodal therapy.
Highlights
Cervical cancer is the eighth deadliest cancer and is responsible for over 20,000 deaths in China annually[1]
Ten mutations occurred in the helical domain (HD), whereas 95 mutations occurred in the kinase domain (KD)
Several rare nonsynonymous base substitutions were identified in our study, some of which have been reported in the Catalog of Somatic Mutations in Cancer (COSMIC) database
Summary
Cervical cancer is the eighth deadliest cancer and is responsible for over 20,000 deaths in China annually[1]. Genes involved in the PI3K pathway represent potential therapeutic targets for cancers, and PIK3CA mutation status may be useful as a biomarker for targeted therapy of cervical cancer. Preclinical and clinical studies have demonstrated that PIK3CA mutations may predict tumor response to PI3K pathway inhibitors[9,10,11,12]. The identification and characterization of cervical cancer patients harboring mutant PIK3CA are important for designing clinical trials investigating PI3K pathway inhibitors. The clinicopathological characteristics and prognostic impact of PIK3CA-mutated cervical cancer have not been well established. It is necessary to conduct PIK3CA mutational analyses in a large cohort of cervical cancer patients. In this study, we investigated the clinicopathological and prognostic relevance of PIK3CA mutations in a large cohort of Chinese patients with surgically resected cervical cancer
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