Prognostic value of tgfb1 protein in endometrioid adenocarcinoma

Eur J Clin Invest. 2013 Jan;43(1):79-90. doi: 10.1111/eci.12017. Epub 2012 Nov 26.

Abstract

Background: Angiogenesis is a prerequisite for tumour development, progression and metastasis; however, its underlying molecular mechanisms in endometrial carcinoma are poorly understood.

Design: In this study, the mRNA and protein expression profiles of two key regulators of angiogenesis, vascular endothelial growth factor (VEGF) and transforming growth factor beta-1 (TGFB1), were evaluated by real-time PCR and western blot analysis in 23 endometrial cancer tissue-paired specimens (malignant vs. adjacent normal tissues). We aimed to investigate whether VEGF and TGFB1 serve as markers of the malignant transformation of the endometrium and whether VEGF or TGFB1 expression can constitute a useful prognostic marker of survival in patients with endometrial carcinoma.

Results: Tissue-pair analysis revealed VEGF transcriptional up-regulation and TGFB1 mRNA down-regulation as the most frequent transcriptional features. VEGF and TGFB1 mRNA were positively correlated (P < 0·001). VEGF protein levels were higher in endometrioid-type tissue pairs (P = 0·047). TGFB1 protein and mRNA levels were negatively correlated (P = 0·042). TGFB1 protein expression was related to survival only in patients with endometrioid adenocarcinoma (P = 0·045).

Conclusions: Tissue-pair mRNA and protein analysis reveals VEGF transcriptional up-regulation and TGFB1 down-regulation that are correlated with the malignant transformation of the endometrium, while post-transcriptional mechanisms control VEGF and TGFB1 protein. TGFB1 protein demonstrated a prognostic value only in endometrioid adenocarcinoma.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Endometrioid / genetics*
  • Carcinoma, Endometrioid / metabolism
  • Carcinoma, Endometrioid / pathology
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • RNA, Neoplasm
  • Real-Time Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • RNA, Neoplasm
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A