Significance of Vasculogenic Mimicry Formation in Gastric Carcinoma

Abstract

Background: The purpose of this study was to evaluate the clinical significance and prognostic roles of vasculogenic mimicry (VM) and elucidate their intrinsic association with molecular markers. Methods: 89 human gastric cancer cases with detailed follow-up and clinicopathologic data were collected. CD34/periodic acid-Schiff double staining was performed to validate the existence of VM. Immunohistochemistry was performed to explore the expression of different molecular factors. Results: VM was observed in 24 gastric cancer patients. They were prone to higher histological grade, hematogenous metastasis, distant recurrence, and chance of progression to stage III or IV (p < 0.05). The VM group had shorter overall and disease-free survival (p < 0.05). VM negativity was independently prognostic for prolonged overall or disease-free survival (p < 0.05). VM was positively associated with levels of matrix metalloproteinase-2, matrix metalloproteinase-9, vascular endothelial growth factor, and vascular endothelial growth factor receptor-1 (p < 0.05), but not with vascular endothelial growth factor receptor-2 (p > 0.05). Conclusion: VM should be regarded as a good marker to indicate pathobiological behaviors of gastric cancer. Using antibodies against matrix metalloproteinases, vascular endothelial growth factor, or vascular endothelial growth factor receptors could be strategies to counteract VM formation.

Melittin Inhibits Hypoxia-Induced Vasculogenic Mimicry Formation and Epithelial-Mesenchymal Transition through Suppression of HIF-1α/Akt Pathway in Liver Cancer

“…To elucidate the mechanisms involved in the reverse effect of melittin on hypoxia-induced VM formation, we first examined the levels of HIF-1 α after melittin treatment. As shown in Figure 2(b), CoCl 2 treatment increased the level of HIF-1 α and its downstream target genes VEGF and MMP-9 that are involved in VM formation and tumor invasion [21]. Melittin suppressed CoCl 2 -induced upregulation of HIF-1 α , VEGF, and MMP-2/9 (Figure 2(b)).…”

Morphological characteristics of vasculogenic mimicry and its correlation with EphA2 expression in gastric adenocarcinoma

“…Ever since the first description of vascular mimicry (VM) in uveal melanoma 2 as a novel paradigm for tumor perfusion, VM has been observed in various types of malignancies 6,7,14 including gastric cancer 9 . In the previous studies, conducted for VM evaluation in gastric cancer specimens, VM was recognized as consisting of periodic acid-Schiff (PAS)-positive and CD31- or CD34-negative vessels, in contrast to classic endothelial blood vessels that are double positive for both PAS and CD31 or CD34 9,25,26 . PAS was shown to stain basement membranes 25,27 and cytoplasm 9,26 of gastric tumor cells lining the external wall of the VM channels without any involvement of CD31/CD34-positive vascular endothelial cells, like the golden standard for VM in solid tumors such as melanoma 2 , breast cancer 8 , and hepatocellular carcinoma 7 .…”

“…In the previous studies, conducted for VM evaluation in gastric cancer specimens, VM was recognized as consisting of periodic acid-Schiff (PAS)-positive and CD31- or CD34-negative vessels, in contrast to classic endothelial blood vessels that are double positive for both PAS and CD31 or CD34 9,25,26 . PAS was shown to stain basement membranes 25,27 and cytoplasm 9,26 of gastric tumor cells lining the external wall of the VM channels without any involvement of CD31/CD34-positive vascular endothelial cells, like the golden standard for VM in solid tumors such as melanoma 2 , breast cancer 8 , and hepatocellular carcinoma 7 . In this study, PAS reaction was observed on the luminal surface and cytoplasm of the gastric tumor cells forming the VM channels.…”

Fact or Fiction, It Is Time for a Verdict on Vasculogenic Mimicry?

“…Similar differences were observed in orbital rhabdomyosarcoma and adrenocorticoid carcinomas (32, 33). Gastric cancer patients with PAS+ structures were prone to present higher histological grade, metastasis, distant recurrence, and 12 months less cumulative OS (34). Similarly, VM+ prostate cancer patients correlated with Gleason score, preoperative prostate-specific antigen (PSA) levels, pathological stage and both lymph node and distant metastasis.…”