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

Journal of Translational Medicine

Research

Aik Seng Ooi¹  Khee Chee Soo²  Ser Yee Lee³  Siok Gek Jacqueline Hwang⁴  Peiyi Chen⁵  Chao-Nan Qian⁶  Jing Chii Wong⁷  Hui Min Bernice Wong⁷  Swe Swe Myint⁷ 

[1] Center for Cancer Genomics and Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan, USA;Department of General Surgery, Singapore General Hospital, Singapore, Singapore;Department of Surgical Oncology, National Cancer Centre, Singapore, Singapore;Department of General Surgery, Singapore General Hospital, Singapore, Singapore;National Cancer Centre Singapore – Van Andel Research Institute, Translational Research Laboratory, Division of Medical Sciences, National Cancer Centre, Singapore, Singapore;Department of Surgical Oncology, National Cancer Centre, Singapore, Singapore;Department of Pathology, Singapore General Hospital, Singapore, Singapore;Department of Statistics & Applied Probability, Faculty of Science, National University of Singapore, Singapore, Singapore;Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan, USA;Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China;National Cancer Centre Singapore – Van Andel Research Institute, Translational Research Laboratory, Division of Medical Sciences, National Cancer Centre, Singapore, Singapore;

关键词: High endothelial venules;    Cancer metastasis;    Angiogenesis;    Lymph nodes;   

DOI  :  10.1186/1479-5876-10-206

 received in 2012-04-03, accepted in 2012-10-02,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundHigh 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.MethodsThis 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.ResultsThe 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© Lee et al.; licensee BioMed Central Ltd. 2012