Micropapillary Lung adenocarcinoma EGFR, K-ras, and BRAF mutational profile

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 06/2009; 131(5):694-700. DOI: 10.1309/AJCPBS85VJEOBPDO
Source: PubMed

ABSTRACT 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.

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    • "If a micropapillary component is the critical one regardless of the percentage, should the primary classification be micropapillary adenocarcinoma, even if it is not predominant? All studies on the topic of the micropapillary component of lung adenocarcinoma in patients in early stages have reported that micropapillary is a poor prognostic subtype.28-31 Further research is needed to answer the question of whether, as in the Gleason score in prostate cancer, a minor pattern contributes a significant amount of prognostic information and whether scores weighting all patterns may be helpful.30 "
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