title: High microvascular density is correlated with high VEGF, iNOS and COX-2 expression in penetrating growth-type early gastric carcinomas.
abstract: OBJECTIVE
  Early gastric carcinomas have two characteristic growth types, superficial spreading (SUP) and penetrating (PEN). Higher mucosal apoptotic activity and lower p21(WAF1/CIP1) expression and submucosal low proliferative activity have been shown in the former, compared with the latter. In order to cast light on whether angiogenesis contributes to these growth patterns, the present immunohistochemical study was performed with cancer tissues.
  
  
  RESULTS
  Of a total of 807 early gastric carcinomas, 30 PEN and 33 SUP type submucosal invasive carcinoma cases were immunohistochemically compared. CD34 positivity, microvascular density (MVD), and expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), but not cyclooxygenase 2 (COX-2) were higher in cancer cells in both mucosal and submucosal layers in PEN than in SUP (P < 0.05). Submucosal MVD in PEN type was greater (P < 0.01) in cases with high than with low Ki67 labelling. Significant correlations were shown between MVD and VEGF, iNOS and COX-2, and VEGF and iNOS expression in the PEN type, but only a weak correlation between iNOS and COX-2 expression was evident with the SUP type.
  
  
  CONCLUSIONS
  Increased MVD in PEN type has an intimate causal relationship to angiogenic factors, high VEGF and iNOS expression. The SUP type, in contrast, has characteristics of low angiogenesis.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ichinoe
authors.forename: T
authors.initials: T
authors.lastname: Mikami
authors.forename: H
authors.initials: H
authors.lastname: Shiraishi
authors.forename: I
authors.initials: I
authors.lastname: Okayasu
mesh_terms: D042501:Angiogenic Proteins / Q000096:biosynthesis*; D018952:Antigens, CD34 / Q000032:analysis; D051546:Cyclooxygenase 2; D005753:Gastric Mucosa / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D042501:Angiogenic Proteins; D018952:Antigens, CD34; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases