Amplification and overexpression of CMET is a common event in brain metastases of non-small cell lung cancer.

Abstract

BACKGROUND:

CMET represents an emerging therapy target for monoclonal antibodies and tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC).

METHODS:

We investigated CMET gene amplification status by fluorescence in-situ hybridization (FISH) and CMET protein expression by immunohistochemistry in a large series of 209 NSCLC brain metastases (BM; 165 adenocarcinoma, 20 squamous cell carcinoma, 11 adenosquamous carcinomas, 11 large cell carcinomas and two large cell neuroendocrine carcinomas) and correlated our results to clinic-pathological parameters and molecular data from previous studies.

RESULTS:

We found CMET gene amplification in 36/167 (21.6%) and CMET protein expression in 87/196 (44.4%) of evaluable BM. There was a strong correlation between the presence of CMET gene amplification and CMET protein expression (P < 0.001, chi-square test). Furthermore, presence of CMET amplification correlated positively with presence of ALK amplifications (P = 0.039, chi-square test) and high HIF1 alpha index (P = 0.013, Mann-Whitney U-test). Neither CMET expression nor CMET gene amplification status correlated with patient outcome parameters or known prognostic factors.

CONCLUSIONS:

CMET overexpression and CMET amplification are commonly found in NSCLC BM and may represent a promising therapeutic target.

• Authors: Matthias Preusser, Berthold Streubel, Anna S Berghoff, Johannes A Hainfellner, Andreas von Deimling, Georg Widhalm, Karin Dieckmann, Adelheid Wöhrer, Monika Hackl, Christoph Zielinski, Peter Birner
• Journal: Histopathology (Histopathology) Vol. 65 Issue 5 Pg. 684-92 (Nov 2014) ISSN: 1365-2559 [Electronic] England
• PMID: 25039982 (Publication Type: Journal Article)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Proto-Oncogene Proteins c-met

Topics

• Adenocarcinoma (pathology)
• Adult
• Aged
• Brain (pathology)
• Brain Neoplasms (pathology, secondary)
• Carcinoma, Adenosquamous (pathology)
• Carcinoma, Large Cell (pathology)
• Carcinoma, Neuroendocrine (genetics)
• Carcinoma, Non-Small-Cell Lung (pathology)
• Carcinoma, Squamous Cell (genetics)
• Female
• Gene Amplification
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Lung Neoplasms (pathology)
• Male
• Middle Aged
• Mutation
• Prognosis
• Proto-Oncogene Proteins c-met (genetics, metabolism)