Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer.

TLDR

Tumor spread through lymphatics is poorly understood, and it is unclear whether cancers induce lymphangiogenesis or merely invade existing peritumoral vessels. The study aimed to quantify tumor lymph vessels in head and neck cancer specimens and correlate their density and proliferation with clinical and pathological variables. Immunostaining for LYVE‑1, CD34, and pKi67 was performed on archival specimens to assess lymph vessel density and proliferation. Hotspots of proliferating intratumoral lymphatics were present in all carcinomas, and high intratumoral lymph vessel density correlated with neck node metastases and infiltrating margins in the oropharyngeal subgroup, while VEGF‑C was elevated in tumors but not linked to lymphatics, suggesting proliferating lymphatics may promote lymph node metastasis.

Abstract

How tumors access and spread via the lymphatics is not understood. Although it is clear that dissemination via the blood system involves hemangiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. To address the issue we quantitated tumor lymph vessels in archival specimens of head and neck cancer by immunostaining for the recently described lymphatic endothelial marker LYVE-1, the vascular endothelial marker CD34, and the pKi67 proliferation marker, correlating lymph vessel density and proliferation index with clinical and pathological variables. Discrete "hotspots" of intratumoral small proliferating lymphatics were observed in all carcinomas, and a high intratumoral lymph vessel density was associated with neck node metastases (n = 23; P = 0.027) and an infiltrating margin of tumor invasion (P = 0.046) in the oropharyngeal subgroup. Quantitation of the lymphangiogenic growth factor vascular endothelial growth factor C by real-time PCR and immunohistochemistry revealed higher levels of mRNA in tumor tissue than in normal samples (n = 8; P = 0.017), but no obvious correlation with intratumoral lymphatics. Our results provide new evidence that proliferating lymphatics can occur in human cancers and may in some cases contribute to lymph node metastasis.