http://www.ncbi.nlm.nih.gov/pubmed/22317764

Clin Cancer Res. 2012 Apr 1;18(7):1947-53. Epub 2012 Feb 8.

Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histologic subtypes and age at diagnosis.

Zhang Y, Sun Y, Pan Y, Li C, Shen L, Li Y, Luo X, Ye T, Wang R, Hu H, Li H, Wang L, Pao W, Chen H.

Source

Authors' Affiliations: Departments of Thoracic Surgery and Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.

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 lungadenocarcinoma.

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 lungadenocarcinomas from female never-smokers. We further compared the clinicopathologic parameters according to mutationalstatus 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.