Prognostic role of insulin-like growth factor receptor-1 expression in small cell lung cancer

APMIS. 2009 Dec;117(12):861-9. doi: 10.1111/j.1600-0463.2009.02545.x.

Abstract

Insulin-like growth factor receptor-1 (IGFR-1) is a cellular membrane receptor which is overexpressed in many tumors and seems to play a critical role in anti-apoptosis. The insulin-like growth factor binding protein-3 (IGFBP-3) is known as a growth suppressor in multiple signaling pathways. The aim of this study was to determine IGFR-1 and IGFBP-3 expression in small-cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. We analyzed IGFR-1 and IGFBP-3 expression in 194 SCLC tissues by immunohistochemical staining. Correlative analyses between IGFR-1 and IGFBP-3 expression in SCLC and clinicopathologic factors were performed. A total of 117 patients had extensive disease (ED) (60.3%) and 77 had limited disease (39.7%). With the median follow-up duration of 49.5 months (24-82 months), the median progression-free survival (PFS) and overall survival (OS) were 7.2 months [95% confidence interval (CI): 6.4-8.0 months] and 14.4 months (95% CI: 12.7-16 months), respectively. IGFR-1 expression was observed in 154 of the 190 tumor tissues, whereas there was no IGFBP-3 expression. Multivariate analysis showed that stage (p < 0.001), response rate (p < 0.001), and lactate dehydrogenase (LDH) levels (p < 0.001) were the independent prognostic factors for PFS, and age (p = 0.014), LDH level (p < 0.001), and stage (p < 0.001) for OS. The IGFR-1 positivity was not associated with PFS or OS in the entire cohort. Subgroup analysis revealed that OS was significantly longer in patients with IGFR-1-positive tissue than IGFR-1-negative tissue in SCLC-ED (p = 0.034). These results suggest that IGFR-1 expression may be useful as a prognostic marker in patients with SCLC-ED.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Disease-Free Survival
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Kaplan-Meier Estimate
  • L-Lactate Dehydrogenase / metabolism*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prognosis
  • Receptor, IGF Type 1 / metabolism*
  • Small Cell Lung Carcinoma / metabolism*
  • Small Cell Lung Carcinoma / pathology

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • L-Lactate Dehydrogenase
  • Receptor, IGF Type 1