Evaluation of premetastatic changes in lymph nodes(pN0) of oral tongue tumour: A prospective observational Study.

Background: Tongue tumors show intra and inter-tumoral heterogenicity with high incidence, relapse and mortality rates necessitating further research.  Recurrence/metastasis that occurs  after surgical resection of primary cancer is often the reason for poor survival in these patients.  Lymph nodes are the most common site of metastasis in tongue tumors. Therefore, premetastatic molecular changes can be best evaluated in lymph nodes which may epitomize the earliest events in the metastasis cascades. The presence of circulating tumor cells(CTCs) in the absence of nodal disease (N0) may represent tumor aggressiveness, suggesting an immune escape which may have high metastatic potential. This trial  was developed  to investigate the earliest pre-metastatic changes which may regulate tumor dormancy and predict metastasis. A better understanding of organotropism or pre-metastatic changes can help in theragnostic, thereby  preventing the outbreak of overt metastasis.  Methods: A single-institutional prospective observational cohort study. This trial will be conducted at a tertiary care Centre (Amrita Institute of Medical Sciences Kochi).  Eligible patients will be enrolled after obtaining informed consent. The dissected lymph nodes will  be subjected to histopathological and immunohistochemical analyses for premetastatic niche (PMN) formation. In addition, circulating tumor cells will be evaluated before treatment and 6 months after treatment. The patients will be followed  up for a period of two years to correlate the findings with the recurrence-free survival. Expected results:  The pre-metastatic changes, if detected will  be  a predictive biomarker. It may help to define future drug targets for metastasis chemoprevention   . CTCs may  define the tumor aggressiveness ,there by  prognostication  and helps in better disease management. Ethics and dissemination: The study has received the following approval: Ethics Committee of Amrita School of Medicine (ECASM-AIMS-2022-048).Trial Registered Prospectively( CTRI/2022/03/041256 ) on 22/03/2022 under Clinical Trial Registry of India.

Premetastatic Niche: A Novel Area for Research in Metastasis with a Potential as Therapeutic Targeting in Oral Cancer.

Premetastatic niche (PMN) concept, introduced by David Lyden and colleagues, is an area that can support cancer cells to nurture in it, but the area itself being bereft of cancerous cells. It provides a microenvironment that is congenial for tumor invasion, endurance, and or proliferation of malignant cells to develop into metastasis. These are noncancerous variations in a tumor-free organ and are the most primitive indications of metastasis. These may have a potential to serve as a diagnostic aid, prognostic biomarkers, and therapeutic target. Nevertheless, there is still no clear elucidation on diverse trails of tumor metastasis via lymphatic or hematogenous route, especially in relationship with the PMN. In this review, contemporary knowledge associated with nodal premetastatic niche formation with forthcoming directions on translational and clinical research is deliberated.