Absence or low IGF-1R-expression in esophageal adenocarcinoma is associated with tumor invasiveness and radicality of surgical resection

J Surg Oncol. 2015 Jun;111(8):1047-53. doi: 10.1002/jso.23923. Epub 2015 Jun 16.

Abstract

Background and objectives: Esophageal adenocarcinoma (EAC) incidence increases, maybe due to increasing prevalences of obesity and diabetes. Concurrent hyperinsulinemia might promote carcinogenesis via the insulin-like growth factor-I receptor (IGF-1R). Expression of the IGF-1R was studied in correlation with diabetes and prognostic parameters.

Methods: Patients with EAC undergoing esophagectomy were prospectively selected. From resected tumors a tissue microarray was constructed. Immunohistochemistry evaluated IGF-1R-expression. Logistic-, cox regression models and survival analyses assessed if diabetes and IGF-1R-expression were associated with prognostic parameters. IGF-1R-expression in normal and Barrett tissues was studied.

Results: Absence or low IGF-1R-expression was associated with T3-, grade 3 tumors and R1 resections (P = 0.001, P = 0.025, P < 0.001, respectively). Logistic regression showed that this was associated with R1 resections (HR 0.24, 95%CI 0.11-0.52). Diabetes was not associated with IGF-1R-expression (P = 0.612). Absence or low IGF-1R-expression decreased 5-year overall survival (P = 0.023) univariably, but not multivariably. IGF-1R-expression was present in Barrett tissues, but diminished in high-grade dysplasia.

Conclusions: Absence or low expression of IGF-1R was associated with high grade- and advanced tumors and less radical resections. IGF-1R might be a tumor marker in Barrett's esophagus since a change in expression patterns was found in the course from normal esophageal tissue to adenocarcinoma.

Keywords: Barrett's esophagus; diabetes mellitus; esophageal adenocarcinoma; insulin-like growth factor-1-receptor expression; prognostic parameters; survival.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Aged
  • Barrett Esophagus / metabolism
  • Barrett Esophagus / pathology
  • Biomarkers, Tumor / biosynthesis*
  • Cell Transformation, Neoplastic / metabolism
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery
  • Esophagectomy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Predictive Value of Tests
  • Prognosis
  • Receptor, IGF Type 1 / biosynthesis*
  • Survival Analysis
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Receptor, IGF Type 1

Supplementary concepts

  • Adenocarcinoma Of Esophagus