The expression of the insulin receptor in gastric cancer correlates with the HER2 status and may have putative therapeutic implications

Steffen M. Heckl, Viva Wiesener, Hans Michael Behrens, Dita Ulase, Sandra Krüger, Christoph Röcken

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: Metabolic reprogramming in gastric cancer (GC) involves not only an alteration of glucose metabolism, but also of insulin receptor (IR) expression. We investigated if (1) GCs express the IR in cancer cells (CC-IR) and vasculature (VIR), (2) IR expression is clinically relevant and may be a novel target of GC treatment. Methods: 467 primary GCs were studied by immunohistochemistry using an IR-specific antibody. CD31-immunostaining ensured the presence of representative intratumoral microvasculature. VIR, and membranous and cytoplasmic CC-IR (mCC-IR, cCC-IR) were evaluated using a modified HistoScore (HScore) and subsequently dichotomized into low or high IR expressions. The IR status was correlated with clinico-pathological patient characteristics, including survival and HER2 status. Results: VIR, mCC-IR, and cCC-IR (HScore > 0) were found in 97.0%, 87.6%, and 95.7% of all GCs. After dichotomization of the HScores, 50.7, 48.8, and 50.3% were classified as VIR-high, mCC-IR-high, and cCC-IR-high, respectively. IR was associated with the Laurén phenotype, tumor localization, local tumor growth, vascular invasion, perineural invasion, tumor budding, mucin phenotype, UICC stage, worse survival, and the HER2 status. On multivariate analysis, VIR status was an independent prognosticator of overall (p = 0.010) and tumor-specific (p = 0.006) patient survival. Conclusions: VIR and CC-IR expressions are frequent in GC, biologically significant and even correlate with the HER2 status, opening avenues for novel putative therapeutic interventions in GC.

Original languageEnglish
Pages (from-to)1130-1142
Number of pages13
JournalGastric Cancer
Volume22
Issue number6
DOIs
Publication statusPublished - 1 Nov 2019

Keywords

  • Cancer treatment
  • Gastric cancer
  • HER-2 Proto-Oncogene Protein
  • Insulin receptor
  • Prognosis

Field of Science

  • 3.2 Clinical medicine
  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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