Consistency between K-ras mutation in peripheral blood and matched tumor tissues detected by PCR-RFLP in Chinese patients with advanced NSCLC and its clinical significance analysis

Abstract

8090 Background: To explore the consistency between K-ras mutation in peripheral blood and matched tumor tissues detected by PCR-RFLP and analyze the prognostic effects of K-ras mutation in peripheral blood in Chinese NSCLC patients (pts) treated by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Methods: Plasma free DNA and matched tumor samples were collected from 264 hospitalized pts in Department of Thoracic Oncology, Peking University School of Oncology between Jan 2005 and Feb 2008. K-ras mutations were detected in coden 12 and 13 of exon 1 by PCR-RFLP and then verificated by sequencing. We compared the mutations in plasma samples and matched tumor tissues which determined an association between K-ras mutation status and clinical outcomes. Results: In 264 pts, K-ras mutation rates in codon 12 and 13 of exons 1 in peripheral blood were 11.36% (30/264) and 0.75% (2/264), also 9.84% (26/264) and 1.13% (3/264) in matched tumor tissues, respectively. Consistency of mutation in codon 12 between in tissues and plasma was 94%(248/264) (Kappa=0.686,P<0.001). Among 107 pts who received EGFR-TKIs treatment, the effective rate(RR), progression-free survival (PFS) and median survival time (MST) in pts with K-ras mutation in plasma DNA were 6.7.%, 2.7 months and 20.5 months, respectively, all which were lower than those of pts with wild type K-ras (32.5%, 23.7 months, 31.5 months; P=0.001, P=0.001, P=0.278, respectively). Conclusions: There is a high consistency of K-ras mutation rate between plasma DNA and matched tumor tissues. K-ras mutation in plasma is able to predict both response and PFS of NSCLC pts with EGFR-TKIs treatment. No significant financial relationships to disclose.