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KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma.
- Source :
-
The American journal of surgical pathology [Am J Surg Pathol] 2016 Dec; Vol. 40 (12), pp. 1579-1590. - Publication Year :
- 2016
-
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.<br />Competing Interests: DISCLOSURES The authors made no disclosures.
- Subjects :
- Adenocarcinoma mortality
Adenocarcinoma pathology
Adenocarcinoma surgery
Adenocarcinoma of Lung
Adult
Aged
Aged, 80 and over
DNA Mutational Analysis
ErbB Receptors genetics
Female
Follow-Up Studies
Humans
Lung Neoplasms mortality
Lung Neoplasms pathology
Lung Neoplasms surgery
Male
Middle Aged
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local mortality
Neoplasm Staging
Pneumonectomy
Prognosis
Retrospective Studies
Survival Analysis
Adenocarcinoma genetics
Biomarkers, Tumor genetics
Lung Neoplasms genetics
Proto-Oncogene Proteins p21(ras) genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-0979
- Volume :
- 40
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The American journal of surgical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 27740967
- Full Text :
- https://doi.org/10.1097/PAS.0000000000000744