Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors

J Clin Endocrinol Metab. 2008 Sep;93(9):3524-31. doi: 10.1210/jc.2008-0065. Epub 2008 Jul 8.


Background: Adrenocortical tumors are heterogeneous neoplasms with incompletely understood pathogenesis. IGF-II overexpression has been consistently demonstrated in adult adrenocortical carcinomas.

Objectives: The objective of the study was to analyze expression of IGF-II and its receptor (IGF-IR) in pediatric and adult adrenocortical tumors and the effects of a selective IGF-IR kinase inhibitor (NVP-AEW541) on adrenocortical tumor cells.

Patients: Fifty-seven adrenocortical tumors (37 adenomas and 20 carcinomas) from 23 children and 34 adults were studied.

Methods: Gene expression was determined by quantitative real-time PCR. Cell proliferation and apoptosis were analyzed in NCI H295 cells and a new cell line established from a pediatric adrenocortical adenoma.

Results: IGF-II transcripts were overexpressed in both pediatric adrenocortical carcinomas and adenomas. Otherwise, IGF-II was mainly overexpressed in adult adrenocortical carcinomas (270.5 +/- 130.2 vs. 16.1 +/- 13.3; P = 0.0001). IGF-IR expression was significantly higher in pediatric adrenocortical carcinomas than adenomas (9.1 +/- 3.1 vs. 2.6 +/- 0.3; P = 0.0001), whereas its expression was similar in adult adrenocortical carcinomas and adenomas. IGF-IR expression was a predictor of metastases in pediatric adrenocortical tumors in univariate analysis (hazard ratio 1.84; 95% confidence interval 1.28-2.66; P = 0.01). Furthermore, NVP-AEW541 blocked cell proliferation in a dose- and time-dependent manner in both cell lines through a significant increase of apoptosis.

Conclusion: IGF-IR overexpression was a biomarker of pediatric adrenocortical carcinomas. Additionally, a selective IGF-IR kinase inhibitor had antitumor effects in adult and pediatric adrenocortical tumor cell lines, suggesting that IGF-IR inhibitors represent a promising therapy for human adrenocortical carcinoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Adenoma / pathology
  • Adolescent
  • Adrenal Cortex Neoplasms / genetics*
  • Adrenal Cortex Neoplasms / pathology
  • Adult
  • Aged
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Infant
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Receptor, IGF Type 2 / genetics*
  • Receptor, IGF Type 2 / metabolism
  • Tumor Cells, Cultured


  • Receptor, IGF Type 2
  • Insulin-Like Growth Factor II