Elevated expressions of SHP2 and GAB2 correlated with VEGF in eutopic and ectopic endometrium of women with ovarian endometriosis

Gynecol Endocrinol. 2020 Sep;36(9):813-818. doi: 10.1080/09513590.2020.1787378. Epub 2020 Jul 3.

Abstract

Aims: Protein tyrosine phosphatase Src-homology-2-domain-containing phosphatase 2 (SHP2) and adaptor protein Grb2-associated binding protein 2 (GAB2) can bind to each other in various signal transduction. However, the expression of SHP2 and GAB2 have not been investigated in endometriosis. The aim of the study was to evaluate the expressions of SHP2 and GAB2, and explore the correlation with Ki67 and VEGF in ovarian endometriosis.Materials and methods: The protein expressions and localizations were assessed immunohistochemically in ectopic, eutopic endometrium and normal endometrium from patients with (n = 30) and without (n = 30) ovarian endometriosis.Results: SHP2 was mainly present in the endometrial glandular epithelium, with increased expression in eutopic endometrium and even higher expression in ectopic endometrium compared to control endometrium (p < .05). GAB2 was immunolocalized in endometrial epithelium and stroma, increasing its expression from control endometrium to eutopic and ectopic endometrium (p < .05). Positive correlation was found between SHP2 and GAB2 in endometrium (p < .01). SHP2 and GAB2 both positively correlated with VEGF (p < .05), but not Ki67 in endometrium.Conclusions: We provide the first evidence that the protein expressions of SHP2 and GAB2 were elevated in ectopic and eutopic endometrium, suggesting GAB2-SHP2 axis regulating VEGF might contribute to the pathomechanism of endometriosis.

Keywords: GAB2; SHP2; VEGF; endometriosis; immunohistochemistry.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Case-Control Studies
  • Endometriosis / metabolism*
  • Endometriosis / pathology
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Epithelium / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Ovarian Diseases / metabolism*
  • Ovarian Diseases / pathology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • GAB2 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11