Sano Rikiya, Kanomata Naoki, Suzuki Soichiro, Shimoya Koichiro, Sato Yasufumi, Moriya Takuya, Shiota Mitsuru
Department of Gynecologic Oncology, Kawasaki Medical School.
Department of Pathology 2, Kawasaki Medical School.
Tohoku J Exp Med. 2017 Oct;243(2):107-114. doi: 10.1620/tjem.243.107.
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 mm) 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.
血管抑制素-1（VASH1）是一种已被确认的血管内皮生长因子（VEGF）诱导血管内皮细胞（ECs）血管生成的负反馈抑制剂。据报道，VASH1不仅在正常组织的内皮细胞中表达，在恶性肿瘤周围的内皮细胞中也有表达。在恶性肿瘤中，VASH1作为一种预后预测标志物也日益受到关注。本研究旨在探讨卵巢癌临床病例中VASH1表达与血管相关因子及各种临床病理结果之间的相关性。我们回顾性分析了58例卵巢癌患者的临床记录。采用免疫组织化学方法检测VASH1及其他血管相关因子（CD31作为微血管密度（MVD）标志物、血管内皮生长因子受体2（VEGFR2）、D2-40作为淋巴管密度标志物）以及Ki67（作为癌细胞增殖标志物）的表达模式。我们研究了免疫组织化学表达与总生存期之间的相关性。VASH1表达模式在国际妇产科联盟（FIGO）分期之间存在显著差异。VASH1阳性血管数量与MVD（斯皮尔曼相关系数（ρ）为0.51，p<0.001）、VEGFR2阳性血管（ρ=0.61，p<0.001）以及Ki67百分比（ρ=0.28，p=0.034）呈显著正相关。Cox单因素分析显示，I-III期VASH1高表达组（>14.6条血管/mm）是一个预后因素（HR=3.3，95%CI=0.4-8.4；p=0.013）。我们的结果表明，卵巢癌中VASH1表达与血管相关因子及Ki67表达显著相关。我们认为VASH1是卵巢癌的一种预后标志物。
