Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma

Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma

RIKIYA SANO,¹ NAOKI KANOMATA,² SOICHIRO SUZUKI,¹ KOICHIRO SHIMOYA,³ YASUFUMI SATO,⁴ TAKUYA MORIYA² and MITSURU SHIOTA¹

¹Department of Gynecologic Oncology, Kawasaki Medical School, Kurashiki, Okayama, Japan
²Department of Pathology 2, Kawasaki Medical School, Kurashiki, Okayama, Japan
³Department of Obstetrics and Gynecology, Kawasaki Medical School, Kurashiki, Okayama, Japan
⁴Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan

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 —— angiogenesis; Ki67; microvessel density; ovarian carcinoma; vasohibin-1

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Tohoku J. Exp. Med., 2017, 243, 107-114

Correspondence: Rikiya Sano, Department of Gynecologic Oncology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.

e-mail: sano_r@med.kawasaki-m.ac.jp