4.4 Article

Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non small cell Lung carcinomas

Journal

HUMAN PATHOLOGY
Volume 44, Issue 6, Pages 975-982

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2012.09.002

Keywords

Insulin-like growth factor-1 receptor; Gene copy number; Non small cell lung carcinoma; Bright-field in situ hybridization

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Funding

  1. National Cancer Center Research and Development Fund, Tokyo, Japan [23-A-2, 23-A-11, 23-A-35]

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Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine ldnase 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-IR gene alteration was rare (8.4%). A statistically significant correlation between IGF-1R expression and positive IGF-1R BISH was observed (gamma = 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. (C) 2013 Elsevier Inc. All rights reserved.

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