KRAS mutation is a significant prognostic factor in early-stage lung adenocarcinoma Journal Article
| Authors: | Kadota, K.; Sima, C. S.; Arcila, M. E.; Hedvat, C.; Kris, M. G.; Jones, D. R.; Adusumilli, P. S.; Travis, W. D. |
| Article Title: | KRAS mutation is a significant prognostic factor in early-stage lung adenocarcinoma |
| Abstract: | The potential clinical impact of KRAS and epidermal growth factor receptor (EGFR) mutations has been investigated in lung adenocarcinomas; however, their prognostic value remains controversial. In our study, we sought to investigate the prognostic significance of driver mutations using a large cohort of early-stage lung adenocarcinomas. We reviewed patients with pathologic early-stage, lymph node-negative, solitary lung adenocarcinoma who had undergone surgical resection (1995 to 2005; stage I/II=463/19). Tumors were classified according to the IASLC/ATS/ERS classification and genotyped by Sequenom MassARRAY system and polymerase chain reaction-based assays. In stage I disease, the Kaplan-Meier method and cumulative incidence of recurrence analyses were used to estimate the probability of overall survival (OS) and recurrence, respectively. Of all, 129 (27%) patients had mutations in KRAS, 86 (18%) in EGFR, 8 (2%) in BRAF, 8 (2%) in PIK3CA, 4 (1%) in NRAS, and 1 (0.2%) in AKT1. EGFR L858R mutation correlated with lepidic predominant histology (P=0.006), whereas exon 19 deletion correlated with acinar predominant histology (P<0.001). EGFR mutations were not detected in invasive mucinous adenocarcinomas (P=0.033). The 5-year OS of patients with KRAS-mutant tumors was significantly worse (n=124; 5-year OS, 63%) than those with KRAS wild-type (n=339; 77%; P<0.001). In solid predominant tumors, KRAS mutations correlated with worse OS (P=0.008) and increased risk of recurrence (P=0.005). On multivariate analysis, KRAS mutation was an independent prognosticator of OS in all patients (hazard ratio, 1.87; P<0.001) and recurrence in solid predominant tumors (hazard ratio, 4.73; P=0.012). In patients with resected stage I lung adenocarcinomas, KRAS mutation was an independent prognostic factor for OS and recurrence, especially in solid predominant tumors. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | adenocarcinoma; epidermal growth factor receptor; lung; kras; prognosis |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 40 |
| Issue: | 12 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2016-12-01 |
| Start Page: | 1579 |
| End Page: | 1590 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000000744 |
| PROVIDER: | scopus |
| PMCID: | PMC5106330 |
| PUBMED: | 27740967 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 December 2016 -- Source: Scopus |
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