2011 Young Surgeon's Award Winner: High Endothelial Venules: A Novel Prognostic Marker in Cancer Metastasis and the Missing Link?

Abstract

Introduction: The extent of lymph nodes (LNs) metastasis is a major determinant for the staging and the most reliable adverse prognostic factor. Primary tumours can induce lymphatics and vasculature reorganisations within sentinel LN before the arrival of cancer cells and these key blood vessels are identified as high endothelial venules (HEV). The alterations of HEV in the presence of cancer, coupled with the increased proliferation rate of the endothelial cells, results in a functional shift of HEV from immune response mediator to blood flow carrier. We aim to evaluate tumour-induced vascularisation in regional LN of cancer patients by studying the morphological and functional alterations of HEV and its correlation to clinico-pathological features. Materials and Methods: This multi-centre study with a prospective database identified 65 consecutive patients with tongue squamous cell carcinoma (SCC) who underwent primary surgical treatment from 2001 to 2005. Immunohistochemical staining for HEV and image analysis were performed and analysed with correlation to the patients’ clinico-pathological features. Results: The total number of HEV is significantly associated to disease-free interval when controlling for the group (P = 0.022) as well as combining both groups as one cohort (P = 0.023). There is also a similar association comparing the HEV parameters to overall survival. Conclusion: Our results suggest that HEV possibly plays a key role in the pathogenesis of lymphatic and subsequent distant metastases and may provide the missing link in cancer metastasis. Confirmation of this hypothesis would offer a novel therapeutic approach to preventing metastasis by blocking the remodeling processes of HEV in LN. Key words: High endothelial venules, Cancer metastasis, Angioegenesis