(Jiang Wei) - Fudan University Fudan University Shanghai Cancer Center Department of Gynecological Oncology
(Xiang Li Bing) - Fudan University Fudan University Shanghai Cancer Center Department of Gynecological Oncology
(Pei Xuan) - Fudan University Fudan University Shanghai Cancer Center Department of Gynecological Oncology
(He Tian Cong) - Fudan University Fudan University Shanghai Cancer Center Department of Gynecological Oncology
(Shen Xu Xia) - Fudan University Shanghai Medical College Department of Oncology
(Wu Xiao Hua) - Fudan University Fudan University Shanghai Cancer Center Department of Gynecological Oncology
(Yang Hui Juan) - Fudan University Fudan University Shanghai Cancer Center Department of Gynecological Oncology
Abstract
Objective: The predictive and prognostic role of KRAS mutations in cervical cancer remains inconclusive. The aim of this study was to explore the clinicopathological and prognostic relevance of KRAS mutations in invasive cervical cancers (ICC).
Methods: Reverse transcription polymerase chain reaction (PCR) and Sanger sequencing were employed to detect KRAS mutations in 876 ICC patients. Quantitative real-time PCR was used to detect human papillomavirus (HPV) 16 and HPV 18.
Results: Non-synonymous mutations of KRAS were identified in 30 (3.4%) patients. These mutations were more common in non-squamous cell carcinoma than in squamous cell carcinoma (SCC) (8.2% vs. 2.2%, respectively, p<0.001) and were associated with HPV 18 infection (p=0.003). The prevalence of mutations was highest (18.2%) in the uncommon histological subtypes followed by adenocarcinoma (AC, 7.3%) and adenosquamous carcinoma (ASC, 5.8%). During the median follow-up of 55 months, compared to patients with wild-type KRAS, a greater percentage of patients with mutant KRAS relapsed (20.0% vs. 42.9%, respectively, p=0.007). The 3-year relapse-free survival was poorer in patients with mutant KRAS than in patients without KRAS mutations (57.1% vs. 81.9%, respectively, p=0.001). Furthermore, the multivariate analysis showed that the presence of a KRAS mutation was an independent predictor for disease recurrence (hazard ratio [HR]=2.064; 95% confidence interval [CI]=1.125?3.787; p=0.019).
Conclusion: KRAS mutations were predominant in non-SCCs of the cervix and were associated with HPV 18 infection. A combination of KRAS mutation detection and HPV genotyping would be useful in identifying patient with poor prognosis for further interventions.
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KRAS, Uterine Cervical Neoplasms, Papillomaviridae, Prognosis
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KRAS mutations were predominant in non-SCCs of the cervix and were associated with HPV 18 infection.