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

Karin E. Finberg, Lecia V. Sequist, Victoria A. Joshi, Alona Muzikansky, Julie M. Miller, Moonjoo Han, Javad Beheshti, Lucian R. Chirieac, Eugene J. Mark, A. John Iafrate

Research output: Contribution to journalArticle

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Abstract

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%) non-mucinous 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.

Original languageEnglish (US)
Pages (from-to)320-326
Number of pages7
JournalJournal of Molecular Diagnostics
Volume9
Issue number3
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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erbB-1 Genes
Mutation
Bronchiolo-Alveolar Adenocarcinoma
Adenocarcinoma
Protein-Tyrosine Kinases
Mucinous Adenocarcinoma
Adenocarcinoma of lung
Neoplasms
Missense Mutation
Codon
Sequence Analysis
Histology
Costs and Cost Analysis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

Cite this

Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features. / Finberg, Karin E.; Sequist, Lecia V.; Joshi, Victoria A.; Muzikansky, Alona; Miller, Julie M.; Han, Moonjoo; Beheshti, Javad; Chirieac, Lucian R.; Mark, Eugene J.; Iafrate, A. John.

In: Journal of Molecular Diagnostics, Vol. 9, No. 3, 01.01.2007, p. 320-326.

Research output: Contribution to journalArticle

Finberg, Karin E. ; Sequist, Lecia V. ; Joshi, Victoria A. ; Muzikansky, Alona ; Miller, Julie M. ; Han, Moonjoo ; Beheshti, Javad ; Chirieac, Lucian R. ; Mark, Eugene J. ; Iafrate, A. John. / Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features. In: Journal of Molecular Diagnostics. 2007 ; Vol. 9, No. 3. pp. 320-326.
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abstract = "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{\%}) non-mucinous 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.",
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