BACKGROUND: The purpose of this study was to characterize insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) expression in patients with nonsmall cell lung cancer (NSCLC). METHODS: A total of 459 patients who underwent curative resection of NSCLC were studied (median follow-up duration, 4.01 years). Expression of the IR and IGF-1R protein in tumor specimens was assessed immunohistochemically using tissue microarrays. RESULTS: The cytoplasmic IR score was higher in patients with adenocarcinoma (ADC) than in those with squamous cell carcinoma (SCC), whereas cytoplasmic IGF-1R score was higher in patients with SCC than those with ADC. Neither IR nor IGF-1R expression was associated with sex, smoking history, or clinical stage. Patients with positive IR or IGF-1R expression levels had poor recurrence-free (RFS) (3.8 vs 3.3 years; 3.8 vs 2.0 years, respectively), but similar overall survival (OS). Patients with high expression levels of IR and IGF-1R had shorter RFS and OS compared with those with low levels of IR and/or IGF-1R expression. Finally, a multivariate analysis revealed the impact of IR, but not of IGF-1R, as an independent predictive marker of NSCLC survival: hazard ratio (HR) for OS, 1.005 (95% confidence interval [CI], 1.001-1.010], HR for RFS, 1.005 (95% CI, 1.001-1.009), when IR score was tested as a continuous variable. CONCLUSIONS: Overexpression of IR predicts a poor survival among patients with NSCLC, especially those with SCC. These results might serve as future guidance to the clinical trials involving IR or IGR-1R targeting agents.
BACKGROUND: The purpose of this study was to characterize insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) expression in patients with nonsmall cell lung cancer (NSCLC). METHODS: A total of 459 patients who underwent curative resection of NSCLC were studied (median follow-up duration, 4.01 years). Expression of the IR and IGF-1R protein in tumor specimens was assessed immunohistochemically using tissue microarrays. RESULTS: The cytoplasmic IR score was higher in patients with adenocarcinoma (ADC) than in those with squamous cell carcinoma (SCC), whereas cytoplasmic IGF-1R score was higher in patients with SCC than those with ADC. Neither IR nor IGF-1R expression was associated with sex, smoking history, or clinical stage. Patients with positive IR or IGF-1R expression levels had poor recurrence-free (RFS) (3.8 vs 3.3 years; 3.8 vs 2.0 years, respectively), but similar overall survival (OS). Patients with high expression levels of IR and IGF-1R had shorter RFS and OS compared with those with low levels of IR and/or IGF-1R expression. Finally, a multivariate analysis revealed the impact of IR, but not of IGF-1R, as an independent predictive marker of NSCLC survival: hazard ratio (HR) for OS, 1.005 (95% confidence interval [CI], 1.001-1.010], HR for RFS, 1.005 (95% CI, 1.001-1.009), when IR score was tested as a continuous variable. CONCLUSIONS: Overexpression of IR predicts a poor survival among patients with NSCLC, especially those with SCC. These results might serve as future guidance to the clinical trials involving IR or IGR-1R targeting agents.
Authors: Paul Haluska; Joan M Carboni; David A Loegering; Francis Y Lee; Mark Wittman; Mark G Saulnier; David B Frennesson; Kimberly R Kalli; Cheryl A Conover; Ricardo M Attar; Scott H Kaufmann; Marco Gottardis; Charles Erlichman Journal: Cancer Res Date: 2006-01-01 Impact factor: 12.701
Authors: Antonio Gualberto; Marisa Dolled-Filhart; Mark Gustavson; Jason Christiansen; Yu-Fen Wang; Mary L Hixon; Jennifer Reynolds; Sandra McDonald; Agnes Ang; David L Rimm; Corey J Langer; Johnetta Blakely; Linda Garland; Luis G Paz-Ares; Daniel D Karp; Adrian V Lee Journal: Clin Cancer Res Date: 2010-07-29 Impact factor: 12.531
Authors: Andrea H Bild; Guang Yao; Jeffrey T Chang; Quanli Wang; Anil Potti; Dawn Chasse; Mary-Beth Joshi; David Harpole; Johnathan M Lancaster; Andrew Berchuck; John A Olson; Jeffrey R Marks; Holly K Dressman; Mike West; Joseph R Nevins Journal: Nature Date: 2005-11-06 Impact factor: 49.962
Authors: Keertik Fulzele; Douglas J DiGirolamo; Zhongyu Liu; Jie Xu; Joseph L Messina; Thomas L Clemens Journal: J Biol Chem Date: 2007-06-06 Impact factor: 5.157
Authors: Mark W Ball; Stephania M Bezerra; Alcides Chaux; Sheila F Faraj; Nilda Gonzalez-Roibon; Enrico Munari; Rajni Sharma; Trinity J Bivalacqua; George J Netto; Arthur L Burnett Journal: Urology Date: 2016-02-18 Impact factor: 2.649
Authors: Kathryn A Gold; Edward S Kim; Diane D Liu; Ping Yuan; Carmen Behrens; Luisa M Solis; Humam Kadara; David C Rice; Ignacio I Wistuba; Stephen G Swisher; Wayne L Hofstetter; J Jack Lee; Waun K Hong Journal: Clin Cancer Res Date: 2013-12-23 Impact factor: 12.531