Ras gene mutations in patients with non-small cell lung carcinoma

Abstract

BACKGROUND: Lung cancer is the leading cause of cancer mortality in most countries, with every year's increasing incidence. At present, surgical resection of early stage disease presents the only treatment associated with a high likelihood of 5-year survival. On the other hand, patients with advanced disease have 5-year survival less than 5%. This poor prognosis is attributable largely to lack of efficient diagnostic methods for early detection and the inability to cure metastatic disease. Therefore, efforts aimed at early identification and interventions in lung cancer are of the highest importance. Mutations in ras oncogenes appear to play a significant role in the development of non-small cell lung carcinoma (NSCLC). Thus, the aim of our study was to determine the incidence of H-ras and K-ras mutations in patients with NSCLC of different histological subtypes: adenocarcinomas (AC), squamous cell carcinomas (SCC), large cell carcinomas (LCC), and adenosquamous carcinomas (AC-SCC). METHODS: We analyzed 41 patients with stage I, II and III of histologically confirmed NSCLC (histological grade 2 and 3). DNA was isolated from frozen tumors by standard phenol-chloroform extraction. Mutations in exon 1 H-ras and K-ras gene were detected by PCR-SSCP method. RESULTS: Mutations in the H-ras gene were found in only 2 of 41 analyzed tumors (4.9%). The both mutations were found in SCC making the overall incidence in this histological subtype 10.5% (2 of 19). K-ras mutations were detected in 31.7% (13 out of 41) of tumors, with higher incidence in tumors of clinical stage I - 45% (9 out of 20). CONCLUSION: Our results indicate that H-ras mutations apparently play an inferior role in lung carcinogenesis. However, mutations in K-ras gene probably present an early event in genesis of NSCLC, and not only in adenocarcinomas, as the majority of previous reports indicate, but also in squamous cell carcinomas as well.