J Gynecol Oncol.  2018 Jan;29(1):e4. 10.3802/jgo.2018.29.e4.

Mutational analysis of KRAS and its clinical implications in cervical cancer patients

• Jiang W
• Xiang L
• Pei X
• He T
• Shen X
• Wu X
• Yang H

• KMID: 2395231
• DOI: http://doi.org/10.3802/jgo.2018.29.e4

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.

Keyword

KRAS; Uterine Cervical Neoplasms; Papillomaviridae; Prognosis

MeSH Terms

Adenocarcinoma
Carcinoma, Adenosquamous
Carcinoma, Squamous Cell
Cervix Uteri
Female
Follow-Up Studies
Human papillomavirus 18
Humans
Multivariate Analysis
Papillomaviridae
Polymerase Chain Reaction
Prevalence
Prognosis
Real-Time Polymerase Chain Reaction
Recurrence
Reverse Transcription
Uterine Cervical Neoplasms*