Expressions of insulin-like growth factor receptor-1 and insulin-like growth factor binding protein 3 in advanced non-small-cell lung cancer

Clin Lung Cancer. 2012 Sep;13(5):385-90. doi: 10.1016/j.cllc.2011.11.009. Epub 2012 Jan 28.

Abstract

Background: The insulin-like growth factor (IGF) pathway plays an important role in cell proliferation, differentiation, and apoptosis, and IGF induces those effects mainly through IGF receptor-1 (IGF-1R). The activities of IGF are strictly regulated by a family of IGF binding proteins (IGFBP), especially IGFBP3, a major serum carrier protein for IGF.

Patients and methods: Between January 2006 and February 2009, in our hospital, 191 patients were histologically diagnosed as having non-small-cell lung cancer (NSCLC), and 74 patients were treated by chemotherapy alone. We examined immunohistochemical expression of both IGF-1R and IGFBP3 in 68 patients who were definitively diagnosed as having adenocarcinoma or squamous cell carcinoma among the 74 patients.

Results: The clinical characteristics of the included patients were as follows: median age was 68 years (range, 29-86 years); men vs. women, 40 vs. 28; stage III vs. IV, 18 vs. 50; performance status 0-1 vs. 2-4, 58 vs. 10; smoker vs. non-smoker, 44 vs. 24; and squamous cell carcinoma vs. adenocarcinoma, 13 vs. 55. Expression of IGF-1R and IGFBP3 was observed in 37 (54%) and 11 patients (16%), respectively. IGF-1R expression was detected more frequently in patients with squamous cell carcinoma (100%) than in patients with adenocarcinoma (44%) (P < .001), although IGFBP3 expression was not significantly associated with any clinical variables. Among all factors, including IGF-1R and IGFBP3 expression, IGF-1R was significantly associated with response to chemotherapy (P = .028) and performance status was significantly associated with overall survival (P < .001).

Conclusions: High sensitivity of IGF-1R to squamous cell carcinoma (100%) in this study and another study encourages the use of IGF-1R antibody in the pathologic diagnosis between squamous cell and non-squamous cell carcinoma when using small biopsy specimens.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Receptor, IGF Type 1 / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Receptor, IGF Type 1