Vasculogenic Mimicry: a New Prognostic Sign of Gastric Adenocarcinoma Man Li Yanjun Gu Zhiguang Zhang Shiwu Zhang Danfang Zhang Ali F. Saleem Xiulan Zhao Baocun Sun Email author Article First Online: 17 December 2009 Received: 31 May 2009 Accepted: 20 October 2009 DOI :
10.1007/s12253-009-9220-7
Cite this article as: Li, M., Gu, Y., Zhang, Z. et al. Pathol. Oncol. Res. (2010) 16: 259. doi:10.1007/s12253-009-9220-7 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 1α (HIF-1α), 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.
Keywords Gastric adenocarcinoma Hypoxia-inducible factor 1α Microvascular density Poorly differentiated Tissue array Vasculogenic mimicry Abbreviations ECM extracellular matrix
EDV endothelium dependent vessel
GAC gastric adenocarcinoma
HIF-1α hypoxia-inducible factor 1 α
MMP matrix metalloproteinase
MV mosaic vessel
MVD microvascular density
PAS periodic acid-Schiff
SI staining index
RBCs red blood cells
VEGF vascular endothelial growth factor
VM vasculogenic mimicry
VMD vasulogenic mimicry density
Man Li and Baocun Sun contributed equally to this work.
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Authors and Affiliations Man Li Yanjun Gu Zhiguang Zhang Shiwu Zhang Danfang Zhang Ali F. Saleem Xiulan Zhao Baocun Sun Email author 1. Department of Pathology, Tianjin Cancer Institute and Hospital Tianjin Medical University Tianjin People’s Republic of China 2. Department of Digestive The Second Hospital of Tianjin Medical University Tianjin People’s Republic of China 3. Department of Surgery Tianjin Medical University Tianjin People’s Republic of China 4. Department of Pathology Tianjin Medical University Tianjin People’s Republic of China