Frequency of Driver Mutations in Lung Adenocarcinoma from Female Never-Smokers Varies with Histologic Subtypes and Age at Diagnosis
- 1 April 2012
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 18 (7), 1947-1953
- https://doi.org/10.1158/1078-0432.ccr-11-2511
Abstract
Purpose: Our previous study revealed that 90% [47 of 52; 95% confidence interval (CI), 0.79–0.96] of Chinese never-smokers with lung adenocarcinoma harbor known oncogenic driver mutations in just four genes EGFR, ALK, HER2, and KRAS. Here, we examined the status of known driver mutations specifically in female never-smokers with lung adenocarcinoma. Experimental Design: Tumors were genotyped for mutations in EGFR, KRAS, ALK, HER2, and BRAF. Data on age, stage, tumor differentiation, histologic subtypes, and molecular alterations were recorded from 349 resected lung adenocarcinomas from female never-smokers. We further compared the clinicopathologic parameters according to mutational status of these genes. Results: Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. In univariate analysis, patients harboring EGFR mutations were significantly older (P < 0.001), whereas patients harboring HER2 mutations were significantly younger (P = 0.036). Higher prevalence of KRAS (P = 0.028) and HER2 (P = 0.021) mutations was found in invasive mucinous adenocarcinoma (IMA). The frequency of EGFR mutations was positively correlated with acinar predominant tumors (P = 0.002). Multivariate analysis revealed that older age at diagnosis (P = 0.013) and acinar predominant subtype (P = 0.005) were independent predictors of EGFR mutations. Independent predictors of HER2 mutations included younger age (P = 0.030) and IMA (P = 0.017). IMA (P = 0.006) and poor differentiation (P = 0.028) were independently associated with KRAS mutations. Conclusions: The frequency of driver mutations in never-smoking female lung adenocarcinoma varies with histologic subtypes and age at diagnosis. These data have implications for both clinical trial design and therapeutic strategies. Clin Cancer Res; 18(7); 1947–53. ©2012 AACR.Keywords
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This publication has 38 references indexed in Scilit:
- Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung CancerThe New England Journal of Medicine, 2010
- Lung Adenocarcinoma From East Asian Never-Smokers Is a Disease Largely Defined by Targetable Oncogenic Mutant KinasesJournal of Clinical Oncology, 2010
- Inhibition of Mutated, Activated BRAF in Metastatic MelanomaThe New England Journal of Medicine, 2010
- Serum estrogen and tumor-positive estrogen receptor-alpha are strong prognostic classifiers of non-small-cell lung cancer survival in both men and womenCarcinogenesis: Integrative Cancer Research, 2010
- Immunohistochemical Expression of Estrogen and Progesterone Receptors Identifies a Subset of NSCLCs and Correlates with EGFR MutationClinical Cancer Research, 2009
- Somatic mutations affect key pathways in lung adenocarcinomaNature, 2008
- Lung cancer in never-smokersJournal of Clinical Pathology, 2006
- EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinibProceedings of the National Academy of Sciences of the United States of America, 2004
- EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib TherapyScience, 2004
- Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to GefitinibThe New England Journal of Medicine, 2004