title: Vasculogenic mimicry: a new prognostic sign of gastric adenocarcinoma.
abstract: Vasculogenic mimicry (VM) has been generally recognized as a new pattern of tumor neovascularization. It presents in many human malignancies. Till now, there is no report about VM in gastric adenocarcinoma (GAC). In this study, we collected 173 paraffin-embedded human GAC samples, with detailed follow-up and clinicopathologic data. CD31/ periodic acid-Schiff (PAS) double staining, immunohistochemical staining of CK8 & 18 and laminin were performed to validate the existence of VM in GAC. Microvascular density (MVD) and vasulogenic mimicry density (VMD) were counted respectively. VM was observed in 40 of the 173 GAC patients, especially in poorly differentiated GAC (P = 0.014). Patients with VM were prone to hematogenous metastasis and distant recurrence compared with patients without VM (P = 0.020, 0.029). Higher VMD values was also associated with hematogenous metastasis (P = 0.003). Immunohistochemical staining index (SI) of hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 were compared between the VM and non-VM group. The SI of four factors were all higher in the VM group than those of non-VM group (P = 0.000, 0.000, 0.004, 0.009, respectively). The Kaplan-Meier survival analysis showed that the VM group has shorter life span compared with non-VM group (P = 0.022). Cox proportional hazards model indicated that the presence of VM and TNM stage were independent predictors of poor prognosis (P = 0.039 and 0.004) for GAC. In conclusion, VM exists in GAC, especially in poorly differentiated GAC. Additionally, it is an unfavorable prognostic indictor for GAC. Hypoxia may play a role in VM formation in GAC.
authors.affiliation: Department of Pathology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Gu
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shiwu
authors.initials: S
authors.lastname: Zhang
authors.forename: Danfang
authors.initials: D
authors.lastname: Zhang
authors.forename: Ali F
authors.initials: AF
authors.lastname: Saleem
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053538:Keratin-18 / Q000096:biosynthesis; D053533:Keratin-8 / Q000096:biosynthesis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053538:Keratin-18; D053533:Keratin-8; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9