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Determining the profiles and parameters for gene amplification testing of growth factor receptors in lung cancer
Author(s) -
Pros Eva,
Lantuejoul Sylvie,
SanchezVerde Lydia,
Castillo Sandra D,
Bonastre Ester,
SuarezGauthier Ana,
Conde Esther,
Cigudosa Juan C,
LopezRios Fernando,
TorresLanzas Juan,
Castellví Josep,
Cajal Santiago Ramon y,
Brambilla Elisabeth,
SanchezCespedes Montse
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28090
Subject(s) - pdgfra , kras , immunostaining , lung cancer , growth factor receptor , fibroblast growth factor receptor 1 , cancer research , biology , cancer , medicine , pathology , oncology , colorectal cancer , receptor , immunohistochemistry , fibroblast growth factor , stromal cell , gist
Growth factor receptors (GFRs) are amenable to therapeutic intervention in cancer and it is important to select patients appropriately. One of the mechanisms for activation of GFRs is gene amplification (GA) but discrepancies arising from the difficulties associated with data interpretation and the lack of agreed parameters confound the comparison of results from different laboratories. Here, we attempt to establish appropriate conditions for standardization of the determination of GA in a panel of GFRs. A NSCLC tissue microarray panel containing 302 samples was screened for alterations at ALK, FGFR1 , FGFR2 , FGFR3 , ERBB2 , IGF1R , KIT , MET and PDGFRA by FISH, immunostaining and/or real‐time quantitative RT‐PCR. Strong amplification was found for FGFR1 , ERBB2 , KIT/PDFGRA and MET , with frequencies ranging from 1 to 6%. Thresholds for overexpression and GA were established. Strong immunostaining was found in most tumors with ERBB2 , MET and KIT amplification, although some tumors underwent strong immunostaining in the absence of GA. KIT and PDFGRA were always coamplified, but only one tumor showed PDGFRA overexpression, indicating that KIT is the main target. Amplification of FGFR1 predominated in squamous cell carcinomas, although the association with overexpression was inconclusive. Interestingly, alterations at ALK, MET, EGFR, ERBB2 and KRAS correlated with augmented levels of phospho‐S6 protein, suggesting activation of the mTOR pathway, which may prove useful to pre‐select tumors for testing. Overall, here, we provide with parameters for the determination of GA at ERBB2, MET, KIT and PDGFRA which could be implemented in the clinic to stratify lung cancer patients for specific treatments.