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

Abstract

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.

Extranodal extension in oral cancer: A role for the nodal microenvironment?

“…In lymph nodes, specialised blood vessels called high endothelial venules (HEV) are found in the paracortex, formed of cuboidal endothelial cells surrounded by FRCs (Figure ). In OSCC lymph nodes with metastatic deposits, an increased density of HEVs has been observed and correlated to poor prognosis . However, HEV density has also been found to be elevated during lymph node enlargement prior to metastatic colonisation and in sentinel lymph nodes (SLN) regardless of metastatic status compared to non‐SLNs .…”

Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

“…The HEV are modified so that they are more dilated and cancer cells and red blood cells are detected within the lumen rather than the expected immune cells in tongue cancer compared with normal, physiological LN (Ref. 78). …”

High resolution MRI for non-invasive mouse lymph node mapping

“…The lymph nodes (LN) can function as “filters” to remove cancer cells from the systemic circulatory system. The regional immune responses within LNs during cancer progression can be an important prognostic indicator and LN response often serves as a critical criterion for evaluating therapeutic response(Deneve et al, 2012; Lee et al, 2012),(Kimber et al, 2000; Helle et al, 2012; Noh et al, 2012). Infection and/or tumor cell migration commonly leads to increases in LN size.…”