Anatomic Pathology: Pulmonary Pathology

• Epidermal growth factor receptor (EGFR)mutation in lung adenocarcinoma and treatment response to tyrosine kinase inhibitors, such as erlotinib, are strongly associated. These are specific mutations, mostly in exon 19 and 21, that target the tyrosine kinase domain of EGFR.

• These somatic mutations in lung adenocarcinoma are associated with Asian descent, young age, female gender, and nonsmoking status; however, these associations cannot be used to select patients for therapy as a significant number of exceptions exist. In one series, the majority of mutations would be missed if only female nonsmokers were tested, and EGFR mutations do occur in cigarette smokers (about one third of cases were in smokers in one series).

• A proportion of large cell carcinomas and adenosquamous carcinomas harbor EGFR mutations. The vast majority of pure squamous carcinomas do not. Within lung adenocarcinomas, histologic patterns do not overall predict EGFR mutations to be useful as a triage for treatment decisions or decisions to perform molecular testing.

• Examination of molecular alterations in lung adenocarcinoma shows about 25% harbor KRAS mutations, 20% EGFR mutations, 5% ALK translocations, and 3% BRAF mutations. These do not appear in the same tumor.

KRAS mutations and BRAF mutations in lung adenocarcinoma are associated with cigarette smoking history, while EGFR and ALK are associated with having never smoked history.

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