title: Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas.
abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. In this study, we included 379 patients who underwent surgical resection (179 diagnosed as having adenocarcinoma [ADC]; 150, squamous cell carcinoma [SCC]; 41, sarcomatoid carcinoma and 9, large cell carcinoma). IGF-1R expression and gene copy number were assessed by immunohistochemistry and bright-field in situ hybridization (BISH), respectively. IGF-1R expression in non-small cell lung carcinoma was observed in 41.4% of samples and was more prevalent in SCC (69.3%) than in ADC (25.1%), large cell carcinoma (33.3%), and sarcomatoid carcinoma (12.2%) (P < .001). Among ADCs, most mucinous ADCs (75%) showed strong membranous staining with the IGF-1R antibody. Compared with protein expression, IGF-1R gene alteration was rare (8.4%). A statistically significant correlation between IGF-1R expression and positive IGF-1R BISH was observed (γ = 0.762, P < .001). IGF-1R-positive tumors were more common in smokers (P = .004), and these tumors were larger (P = .006) than the IGF-1R-negative tumors. IGF-1R BISH positivity was not correlated with any clinicopathologic factor. IGF-1R expression and IGF-1R BISH positivity were not correlated with overall survival. IGF-1R is highly expressed in SCC and mucinous ADC, although copy number alterations in the IGF-1R gene were rare. These findings may have important implications for future anti-IGF-1R therapeutic approaches.
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan. ktsuta@ncc.go.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mimae
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nitta
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Akiko M
authors.initials: AM
authors.lastname: Maeshima
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Koh
authors.initials: K
authors.lastname: Furuta
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D017526:Receptor, IGF Type 1