Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma

Tohoku J Exp Med. 2017 Oct;243(2):107-114. doi: 10.1620/tjem.243.107.

Abstract

Vasohibin-1 (VASH1) is an identified negative feedback inhibitor of angiogenesis induced by vascular endothelial growth factor (VEGF) in vascular endothelial cells (ECs). Expression of VASH1 has been reported not only in ECs of normal tissue, but also in ECs surrounding malignant tumors. In malignant tumors, VASH1 is also gaining attention as a prognosis prediction marker. The aim of this study is to investigate the correlation between VASH1 expression and vascular-related factors and various clinicopathological outcomes in clinical cases of ovarian carcinoma. We retrospectively analyzed clinical records of 58 patients with ovarian carcinoma. The expression patterns of VASH1 and other vascular-related factors (CD31 as markers of microvessel density (MVD), VEGF receptor type 2 (VEGFR2), D2-40 as markers of lymphovessel density), and Ki67 (as proliferation markers of cancer cells) were examined immunohistochemically. We studied the correlation between immunohistochemical expression and overall survival. VASH1 expression pattern significantly differed between Federation of Obstetrics and Gynecology (FIGO) Stages. Numbers of VASH1-positive vessels had a significant positive correlation with MVD (Speaman's correlation coefficient (ρ) was 0.51, p < 0.001), VEGFR2-positive vessels (ρ = 0.61, p < 0.001), and percentage of Ki67 (ρ = 0.28, p = 0.034). The Cox univariable analyses revealed that the group of high VASH1 expression (> 14.6 vessels per mm2) at Stages I-III is a prognostic factor (HR = 3.3, 95%CI = 0.4-8.4; p = 0.013). Our results indicate that VASH1 expression in ovarian carcinoma is significantly associated with vascular-related factors and Ki67 expression. We propose that VASH1 is a prognostic marker in ovarian carcinoma.

Keywords: Ki67; angiogenesis; microvessel density; ovarian carcinoma; vasohibin-1.

MeSH terms

  • Adult
  • Aged
  • Cell Cycle Proteins / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Young Adult

Substances

  • Cell Cycle Proteins
  • VASH1 protein, human