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Changes in specialized blood vessels in lymph nodes and their role in cancer metastasis

Ser Yee Lee123*, Chao-Nan Qian45, Aik Seng Ooi6, Peiyi Chen7, Hui Min Bernice Wong2, Swe Swe Myint2, Jing Chii Wong2, Siok Gek Jacqueline Hwang8 and Khee Chee Soo13

Author Affiliations

1 Department of General Surgery, Singapore General Hospital, Singapore, Singapore

2 National Cancer Centre Singapore – Van Andel Research Institute, Translational Research Laboratory, Division of Medical Sciences, National Cancer Centre, Singapore, Singapore

3 Department of Surgical Oncology, National Cancer Centre, Singapore, Singapore

4 Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan, USA

5 Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China

6 Center for Cancer Genomics and Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan, USA

7 Department of Statistics & Applied Probability, Faculty of Science, National University of Singapore, Singapore, Singapore

8 Department of Pathology, Singapore General Hospital, Singapore, Singapore

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Journal of Translational Medicine 2012, 10:206  doi:10.1186/1479-5876-10-206

Published: 4 October 2012



High endothelial venules (HEV) have been recognized to play a role in metastasis by its changes seen in the cancer microenvironment of lymph nodes (LN) and solid cancers. Squamous cell carcinoma (SCC) of the tongue is a prevalent tumor of the head and neck region with high propensity for LN metastasis. The extent of LN metastasis is the most reliable adverse prognostic factor. Primary tumors can induce vasculature reorganization within sentinel LN before the arrival of tumor cells and HEV represents these remodelled vessels. This study aims to evaluate the cancer induced vascular changes in regional lymph nodes (LN) of patients by studying the morphological and functional alterations of HEV and its correlation with clinical outcome and pathological features.


This study was based on 65 patients with SCC tongue who underwent primary surgical treatment including neck dissection. The patients were categorized into 2 groups based on the presence of malignancy in their cervical lymph nodes. A review of the patients' pathological and clinical data was performed from a prospective database. Immunohistochemical staining of the tissue blocks for HEV and high-power-field image analysis were performed and analyzed with correlation to the patients' clinical and pathological features.


The total number of HEV was found to be significantly associated to disease-free interval. There was a similar association comparing the HEV parameters to overall survival. The density of abnormal HEV was significantly higher in patients with established metastases in their lymph nodes and HEV was shown to be a better prognosis factor than conventional tumor staging. The HEV morphological metamorphosis demonstrates a spectrum that correlates well with disease progression and clinical outcome.


The results suggest that the HEV displays a spectrum of morphological changes in the presence of cancer and LN metastasis, and that HEV is possibly involved in the process of cancer metastasis. We revealed the relationship of HEV and their metamorphosis in pre-metastatic and metastatic environments in regional lymph nodes of tongue cancer patients in relation to clinical outcomes. The significant observation of modified dilated HEV containing red blood cells in lymph nodal basin of a cancer suggests the shifting of its function from one primarily of immune response to that of a blood carrying vessel. It also demonstrated potential prognostic value. More studies are needed to elucidate its potential role in cancer immunotherapy and as a potential novel therapeutic approach to preventing metastasis by manipulating the remodelling processes of HEV.

High endothelial venules; Cancer metastasis; Angiogenesis; Lymph nodes