Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features.

Published

Journal Article

Somatic mutations in the epidermal growth factor receptor gene (EGFR) are detected in a subset of lung adenocarcinomas, particularly bronchioloalveolar carcinoma (BAC) and adenocarcinoma with bronchioloalveolar features (AWBF), and correlate with clinical response to tyrosine kinase inhibitors (TKIs). In contrast, lung adenocarcinomas refractory to TKIs often have activating mutations in KRAS but lack EGFR mutations. Some adenocarcinomas have mucinous histology, but the clinical and molecular significance of the mucinous pattern is less well studied. We analyzed 43 BAC and AWBF tumors submitted for EGFR mutation testing to identify histopathological features that predicted EGFR or KRAS mutations. EGFR mutations were detected in 14 of 30 (47%) nonmucinous tumors, whereas 0 of 13 mucinous tumors harbored an EGFR mutation (P = 0.003). Missense mutations in KRAS codon 12 were detected in six of seven (86%) mucinous adenocarcinomas but only 3 of 18 (17%) nonmucinous adenocarcinomas (P = 0.003). Thus, in BAC/AWBF mucinous differentiation was significantly correlated with the absence of EGFR mutation and presence of KRAS mutation, suggesting that mucinous BACs/AWBFs are unlikely to respond to TKIs. Therefore, our data suggest that EGFR sequence analysis could be avoided in BAC/AWBF when true mucinous morphology is identified, avoiding the associated testing costs.

Full Text

Cited Authors

  • Finberg, KE; Sequist, LV; Joshi, VA; Muzikansky, A; Miller, JM; Han, M; Beheshti, J; Chirieac, LR; Mark, EJ; Iafrate, AJ

Published Date

  • July 2007

Published In

Volume / Issue

  • 9 / 3

Start / End Page

  • 320 - 326

PubMed ID

  • 17591931

Pubmed Central ID

  • 17591931

Electronic International Standard Serial Number (EISSN)

  • 1943-7811

International Standard Serial Number (ISSN)

  • 1525-1578

Digital Object Identifier (DOI)

  • 10.2353/jmoldx.2007.060182

Language

  • eng