Micropapillary lung adenocarcinoma: EGFR, K-ras, and BRAF mutational profile.

Micropapillary lung adenocarcinoma (MPA) has been reported as an aggressive variant of adenocarcinoma, frequently manifesting at high stage with a poor prognosis. We analyzed the clinical and molecular profile of 15 primary MPAs for K-ras, EGFR, and BRAF mutations and performed fluorescence in situ hybridization for EGFR amplification. In our study, 11 (73%) of 15 MPAs harbored mutually exclusive mutations: 5 (33%) K-ras, 3 (20%) EGFR, and 3 (20%) BRAF. Mutations in all 3 genes occurred in patients with a smoking history and tumors with mucinous differentiation and secondary lepidic, acinar, and solid growth, suggesting that in a Western population, cytomorphologic correlation with genetic mutations is more unpredictable than in Japanese cohorts. We conclude that K-ras, EGFR, and BRAF mutations are disproportionately seen in adenocarcinomas of lung with a dominant micropapillary growth pattern compared with conventional adenocarcinoma in our institutional experience.