title: Can mutations of EGFR and KRAS in serum be predictive and prognostic markers in patients with advanced non-small cell lung cancer (NSCLC)?
abstract: The status of epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) mutations has been used widely in management of patients with non-small cell lung cancer (NSCLC). However, it may be difficult to get tumor tissues for analyzing the status of EGFR and KRAS mutation in large proportion of patients with advanced disease. We obtained pairs of tumor and serum samples from 57 patients with advanced NSCLC, between March 2006 and January 2009. EGFR mutation status from tumor samples and KRAS mutation status from serum samples were analyzed by genomic polymerase chain reaction and direct sequence, and EGFR mutation status from serum samples was determined by the peptide nucleic acid-locked nucleic acid PCR clamp. EGFR mutations were detected in the serum samples of 11 patients and in the tumor samples of 12 patients. Fourteen patients revealed (?) KRAS mutation in the serum sample. EGFR mutation status in the serum and tumor samples was consistent in 50 (87.7 %) of the 57 pairs (correlation index 0.62, p < 0.001). Only 5 of 57 (8.7 %) patients showed mutation of both EGFR and KRAS in serum sample. Twenty-two of 57 patients (38.5 %) received EGFR-TKIs as any line therapy. The response for EGFR-TKIs was significantly associated with EGFR mutations in both tumor samples and serum samples (p < 0.05). The status of KRAS mutation in serum was not predictive for the response of EGFR-TKI (p > 0.05). There was no significant difference in OS according to the status of EGFR mutations in both serum and tumor samples (p > 0.05) and KRAS mutations in serum samples (p > 0.05). The status of EGFR and KRAS mutation in serum was not prognostic in patients with advanced NSCLC. However, the clinical usefulness of EGFR mutation of serum as a selection marker for EGFR-TKIs sensitivity in NSCLC might be allowed, not KRAS mutation.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, South Korea.
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Jae Sook
authors.initials: JS
authors.lastname: Sung
authors.forename: Uk Hyun
authors.initials: UH
authors.lastname: Jo
authors.forename: Kyong Hwa
authors.initials: KH
authors.lastname: Park
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Shin
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins