Genetic alterations in the K-Ras gene influence the prognosis in patients with cervical cancer treated by radiotherapy

Abstract

Introduction: A high incidence of K-Ras mutations has been identified in a variety of human cancers, especially in codon 12, 13, and 61. Nevertheless, the presence of K-Ras mutations in cervical cancer remains controversial. The aim of this study was to investigate possible mutations in exon 1 and 2 of the K-Ras gene and to assess whether K-Ras mutation status had prognostic and predictive significance and were linked to clinicopathological parameters. Methods: Genomic DNA from 107 patients with cervical cancer, treated with radiochemotherapy, were examined for mutations in the coding exons 1 and 2, including exon/ intron borders of the K-Ras gene using single-stranded conformation polymorphism and sequence analyses. Results: K-Ras mutations were detected in 11 patients (10%). Seven tumors showed a mutation in codon 59, 3 tumors in codon 38, and 1 tumor in codon 13. In 6 of the cases with a mutation in codon 59, an additional alteration located in codon 65 was found. Patients with K-Ras mutations had significantly worse recurrence-free survival (P = 0.03), and an association between K-Ras status and distant metastases was also seen (P = 0.04). Conclusions: The present data indicate that K-Ras mutations are relatively uncommon in cervical cancer but associates with poorer prognosis, especially in the subset of squamous cell carcinomas. There is a need for new markers in cervical cancer to improve individual treatment, but whether K-Ras mutation status is a potential biomarker in this situation needs further investigations in larger tumor series and in more regions of the K-Ras gene. Copyright © 2010 by IGCS and ESGO.