Insulin-like growth factor receptor 1 (IGF1R) gene copy number is associated with survival in operable non-small-cell lung cancer: a comparison between IGF1R fluorescent in situ hybridization, protein expression, and mRNA expression.
OBJECTIVE
The purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non-small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis.


METHODS
One hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181).


RESULTS
IGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis.


CONCLUSIONS
IGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.
Dziadziuszko
Rafal
R
University of Colorado Cancer Center, PO Box 6511, Mail Stop 8111, Aurora, CO 80045, USA.
Merrick
Daniel T
DT
Witta
Samir E
SE
Mendoza
Adelita D
AD
Szostakiewicz
Barbara
B
Szymanowska
Amelia
A
Rzyman
Witold
W
Dziadziuszko
Katarzyna
K
Jassem
Jacek
J
Bunn
Paul A
PA
Varella-Garcia
Marileila
M
Hirsch
Fred R
FR
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D018287:Carcinoma, Large Cell / Q000737:chemistry / Q000235:genetics / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D013510:Pulmonary Surgical Procedures; D012333:RNA, Messenger / Q000032:analysis*; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D012333:RNA, Messenger; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1