Vasculogenic mimicry contributes to lymph node metastasis of laryngeal squamous cell carcinoma

Abstract

Background: Survival of laryngeal squamous cell carcinoma (LSCC) patients has remained unchanged over recent years due to its uncontrolled recurrence and local lymph node metastasis. Vasculogenic mimicry (VM) is an alternative type of blood supplement related to more aggressive tumor biology and increased tumor-related mortality. This study aimed to investigate the unique role of VM in the progression of LSCC.

Methods: We reviewed clinical pathological data of 203 cases of LSCC both prospectively and retrospectively. VM and endothelium-dependent vessel (EDV) were detected by immunohistochemistry and double staining to compare their different clinical pathological significance in LSCC. Survival analyses were performed to assess their prognostic significance as well.

Results: Both VM and EDV existed in LSCC type of blood supply. VM is related to pTNM stage, lymph node metastasis and pathology grade. In contrust, EDV related to location, pTNM stage, T stage and distant metastasis. Univariate analysis showed VM, pTNM stage, T classification, nodal status, histopathological grade, tumor size, and radiotherapy to be related to overall survival (OS). While, VM, location, tumor size and radiotherapy were found to relate to disease free survival (DFS). Multivariate analysis indicated that VM, but not EDV, was an adverse predictor for both OS and DFS.

Conclusions: VM existed in LSCC. It contributed to the progression of LSCC by promoting lymph node metastasis. It is an independent predictors of a poor prognosis of LSCC.

Figure 1

Identifying VM and EDV in human sample of LSCC by CD31and PAS double staining. A.) The VM channel (black arrow) in human sample is formed by laryngeal cancer cells. There are red blood cells in the center of the channel. PAS-positive substances line the channel and form a basement membrane-like structure (pink). Note the absence of necrosis and hemorrhage in the tumor tissue near the VM channel (original magnification: ×400). B.) Endothelium-dependent vessels (black arrows) are lined by spindle-shape endothelial cells, which are stained by CD31 (brown). The vessels' basement membrane is positive for PAS staining (pink) (original magnification: ×400).

Figure 2

The curves of overall survival and disease-free survival according to VM and MVD in 203 patients with LSCC. A.) Overall survival according to VM positive and VM negative (p = 0.014). B.) Overall survival according to high MVD (MVD≥17.53) and low MVD (MVD＜17.53) (p = 0.772). 17.53 was the average MVD of 203 cases of LSCC patients. C.) Disease-free survival according to VM positive and VM negative (p = 0.011). D.) Disease-free survival according to high MVD and low MVD (p = 0.847).