title: Frequent overexpression of ErbB--receptor family members in brain metastases of non-small cell lung cancer patients.
abstract: The ErbB receptor family has been implicated in brain metastases (BM) formation in various cancer types and specific targeted therapies are available. We investigated the overexpression of EGFR, HER2 and HER3 in BM of non-small cell lung cancer (NSCLC) patients to get a better insight on pathobiology of BM and potential drugable targets. We performed immunohistochemical analysis of EGFR, HER2 and HER3 on tissue microarrays of 131 NSCLC-BM. Fifty-one of 131 (38.9%) specimens were considered as positive for EGFR overexpression, 12/131 (9.2%) for HER2 and 27/131 (20.6%) for HER3 respectively. Sixty-nine of 131 (52.7%) of the cases showed overexpression of at least one marker. Four of 131 (3.1%) were positive for all three markers. Strong correlation was observed between HER2 and HER3 overexpression (p = 0.009; Chi-square test after Bonferroni-Holmes correction). No statistically significant correlation of EGFR, HER2 or HER3 overexpression with clinico-pathological parameters including overall survival times was observed. We observed overexpression of ErbB receptor family members, which represent established therapeutic targets in various primary tumours, in approximately half of NSCLC-BM. Further studies should investigate the role of the ErbB pathway in development of and as a therapeutic target in BM of NSCLC patients.
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, Vienna, Austria.
authors.forename: Anna Sophie
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Manuel
authors.initials: M
authors.lastname: Magerle
authors.forename: Ayseguel
authors.initials: A
authors.lastname: Ilhan-Mutlu
authors.forename: Carina
authors.initials: C
authors.lastname: Dinhof
authors.forename: Georg
authors.initials: G
authors.lastname: Widhalm
authors.forename: Karin
authors.initials: K
authors.lastname: Dieckman
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
authors.forename: Adelheid
authors.initials: A
authors.lastname: Wöhrer
authors.forename: Monika
authors.initials: M
authors.lastname: Hackl
authors.forename: Sabine
authors.initials: S
authors.lastname: Zöchbauer-Müller
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary* / Q000601:surgery / Q000628:therapy; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D020893:Receptor, ErbB-3 / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human
keywords: Brain metastases; EGFR; HER2; HER3; lung cancer; non-small cell lung cancer