title: Angiogenesis and vascular maturation in neuroendocrine tumors.
abstract: Neuroendocrine tumors (NETs) are highly vascularized, but the process of proliferation and maturation of vascular structures during tumor development and progression has remained unknown. We examined the structural alterations of intratumoral blood vessels in human gastroenteropancreatic NET. Microvessel density was evaluated using the endothelial cell markers vasohibin-1 (VASH-1), CD31, and endoglin in 135 cases. Double immunohistochemistry staining was performed to localize endothelium and pericytes on the same vessels using the pericyte marker nestin. The ratio of Ki-67/CD31 was significantly correlated with that of VASH-1/CD31 positivity (P<.001), indicating that the ratio of VASH-1/CD31 also reflects the status of neovascularization in NET. This ratio was higher in NET than in its nonneoplastic counterpart (P=.10) and tended to increase according to World Health Organization (WHO) grade, although the differences were not statistically significant (P=.32). The ratio of VASH-1/nestin-positive vessels, representing the maturation of neovessels, was also significantly higher in NET than in its nonneoplastic counterparts (P=.003). Among WHO grades, the ratio increased from grade 1 to grade 2 (P=.36) and decreased in neuroendocrine carcinoma (P=.34). Our results demonstrated that VASH-1/CD31 can be an ideal immunohistochemical marker for characterizing neovascularization in NET. The VASH-1/CD31 content increased with WHO grade, and the vessels covered by pericytes decreased in higher grades. These structural changes in the vessels are considered to play an important role in inducing tumor-cell proliferation.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Yazdani
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai 980-8575, Japan. Electronic address: kasajima@patholo2.med.tohoku.ac.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kasajima
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Pathology, Tohoku University Hospital, Sendai 980-8575, Japan; Department of Surgery, Tohoku University Hospital, Sendai 980-8575, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tamaki
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai 980-8575, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Fujishima
authors.affiliation: Department of Surgery, Tohoku University Hospital, Sendai 980-8575, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ohtsuka
authors.affiliation: Department of Surgery, Tohoku University Hospital, Sendai 980-8575, Japan.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Motoi
authors.affiliation: Department of Surgery, Tohoku University Hospital, Sendai 980-8575, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai 980-8575, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Pathology, Tohoku University Hospital, Sendai 980-8575, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis / Q000096:biosynthesis; D004067:Digestive System Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000098:blood supply* / Q000473:pathology*; D020286:Pericytes / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C493181:VASH1 protein, human
keywords: Neovascularization; Neuroendocrine tumor; Pericyte; Vasohibin-1