A novel definition of microvessel density in renal cell carcinoma: Angiogenesis plus vasculogenic mimicry

Abstract

The present study proposed the novel concept of total microvessel density (TMVD), which is the combination of the MVD and the vasculogenic mimicry (VM) status, and evaluated its clinical significance in patients with renal cell carcinoma (RCC). For that purpose, tumor samples from 183 patients with primary RCC were examined by CD34 single or periodic acid Schiff (PAS)/CD34 dual histology staining. MVD and VM were determined according to previous literature. Clinical information (tumor stage and grade, and duration of survival) was retrieved and analyzed. Survival information and VM-associated gene expression data of patients with RCC were also retrieved from The Cancer Genome Atlas (TCGA) database and the clinical significance of each individual gene was analyzed. The results indicated that MVD exhibited obvious differences among patients with RCC; however, it was not correlated with the stage/grade or length of survival in patients with RCC. In total, 81 patients (44.3%) were CD34(-)/PAS(+) and defined as VM(+), and they had a significantly shorter survival compared with that of VM(-) patients (P=0.0002). VM was not associated with MVD. TMVD was able to distinguish between patients with high and low MVD in terms of survival, thus TMVD was better compared with MVD alone at distinguishing between patients with different survival prognoses. TCGA data analysis revealed that among the VM-associated genes, nodal growth differentiation factor, caspase-3, matrix metalloproteinase-9 and galectin-3 had a statistically significant impact on the overall/disease-free survival of patients with RCC. In conclusion, the TMVD concept may be more appropriate and sensitive compared with the MVD or VM alone in predicting tumor aggressiveness and patient survival, particularly in RCC, which is a highly vascularized, VM-rich neoplasm, and certain VM formation-associated genes are negatively associated with the survival of patients with RCC.

Microbial metabolite deoxycholic acid promotes vasculogenic mimicry formation in intestinal carcinogenesis

“…CD34/PAS double staining is a method commonly used to verify the formation of VM in tumor tissue 26 . Briefly, after immunohistochemical staining for CD34 (Abcam, 1:100 dilution) was completed, sections were stained with periodic acid solution for 10 minutes, then rinsed twice with distilled water for 3 minutes.…”

“…CD34/PAS double staining is a method commonly used to verify the formation of VM in tumor tissue. 26 Briefly, after immunohistochemical staining for CD34 (Abcam, 1:100 dilution) was completed, sections were stained with periodic acid solution for 10 minutes, then rinsed twice with distilled water for 3 minutes. Then schiff solution was applied to the sections for 20 minutes prior to rinsing with distilled water, counterstaining with hematoxylin, and dehydrating with ethanol gradient.…”

Metastasis, an Example of Evolvability

“…This condition induces the initialization of the VEGF cascade [9], ending in neoangiogenesis. A new definition of microvessel density in CCRCC has been recently published [22]. These authors consider the sum of classical microvessel density and vasculogenic mimicry as the total microvessel density and correlate this sum with prognosis [22].…”

“…A new definition of microvessel density in CCRCC has been recently published [22]. These authors consider the sum of classical microvessel density and vasculogenic mimicry as the total microvessel density and correlate this sum with prognosis [22]. Since these neoplasms are highly vascularized, the antiangiogenic tyrosine-kinase inhibitors have had a relevant role in the therapeutic armamentarium, particularly in metastatic patients [23].…”

Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment

“…Metronomic Chemotherapy to Target Endothelial, Cancer, and Cancer Stem Cells A systematic review of preclinical studies has confirmed the significant relationship between reduced tumor vascularization and inhibition of tumor development, thus highlighting the importance of vascular efficiency [76]. However, a microvascular density analysis cannot distinguish between angiogenic and non-angiogenic tumors, therefore the histopathological growth pattern of tumors must be taken into account [77] or the term "microvessel density" redefined [78,79]. Two tumor phenotypes have been distinguised in murine tumor models and tumor specimens from patients based on the vascular/stromal architecture ratio, which are known as "tumor vessel" and "stromal vessel" and are sensitive or refractory to the VEGFR-2-blocking antibody DC101, respectively [80].…”