title: Expression of vasohibin as a novel endothelium-derived angiogenesis inhibitor in endometrial cancer.
abstract: We have previously reported on vasohibin as a novel endothelium-derived vascular endothelial growth factor (VEGF)-inducible inhibitor of angiogenesis. The aim of our present study was to define the role of vasohibin in endometrioid endometrial adenocarcinoma. We collected 78 sections of endometrial carcinoma for assessment using immunohistochemistry. Twenty-seven were well differentiated (G1), 25 were moderately differentiated (G2), and 26 were poorly differentiated endometrioid adenocarcinomas (G3). We also included 12 sections of normal cyclic endometria, six of which were in the proliferative phase and six were in the secretory phase. We investigated the expression of vasohibin, and compared it to VEGF receptor-2 (VEGFR-2: KDR/flk-1), CD34, Ki-67, VEGF-A, and D2-40 (as a lymphatic vessel marker). We assessed the ratio of vasohibin- and VEGFR-2-positive vessels in the stroma of endometrial carcinoma. Immunohistochemical assessment was classified as negative or positive based on staining intensity. Vasohibin was selectively expressed on vascular endothelial cells in both cyclic endometria and endometrial carcinomas. Vasohibin was highly expressed in the normal functional endmetrium of the secretory phase, especially in the spiral artery, and was highly expressed in all grades of endometrioid adenocarcinomas. The stromal endothelial cells in G3 expressed vasohibin and VEGFR-2 more frequently than these in G1. In endometrioid adenocarcinomas, there was a significant correlation between the expression percentage of vasohibin and that of VEGFR-2 (P < 0.0001, r(2) = 0.591). This is the first study to elucidate the correlation between expression of vasohibin in the stromal endothelial cells and that of VEGFR-2 in human carcinomas.
authors.affiliation: Department of Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagase
authors.forename: Tadao
authors.initials: T
authors.lastname: Takano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niikura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D018797:Cell Cycle Proteins; C493181:VASH1 protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2