IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer

Virchows Arch. 2003 Aug;443(2):139-45. doi: 10.1007/s00428-003-0856-5. Epub 2003 Jul 5.


Insulin-like growth factors (IGF-1 and IGF-2) and the IGF-1 membrane receptor (IGF-1R) have been found to play a critical role in the carcinogenesis of several tumors, among them colorectal cancer (CRC). To study the prognostic impact of these molecules, a total number of 713 cases of CRC were examined for the expression of IGF-1, IGF-2, and IGF-1R. The results were correlated with other clinicopathological data and clinical follow-up. IGF-1 expression was noted in 53 (7.5%), IGF-2 in 88 (12.6%), and IGF-1R in 698 (99.6%) of the cases. There were significant associations between the two growth factors ( P<0.00001), between IGF-1 and Ki-67 proliferation activity ( P<0.05), and between IGF-2 and tumor stage ( P<0.005). IGF-2 positivity was significantly correlated to a worse clinical outcome ( P<0.005) only in univariate, but not in multivariate, survival analysis. A similar trend was obtained for patients with IGF-1-positive CRC, but reached statistical significance only in limited tumor stages (pT1/pT2; P<0.01). Although the synchronous expression of IGF-1, IGF-2, and IGF-1R in a subset of CRC is consistent with an auto-/paracrine loop of cancer cell autostimulation, the prognostic effect of IGF-1 and IGF-2 expression seems to be of limited value. However, the identification of IGF-positive CRC might be beneficial for predictive reasons, as new molecular therapeutic approaches are aimed at the IGF system and related pathways.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Insulin-Like Growth Factor II / metabolism*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Receptor, IGF Type 1 / metabolism*
  • Survival Analysis
  • Survival Rate


  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins
  • myotrophin
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1