Establishing Fascin over-expression as a strategic regulator of neoplastic aggression and lymph node metastasis in oral squamous cell carcinoma tumor microenvironment.

Introduction: Oral squamous cell carcinoma (OSCC) has an aggressive behaviour with high incidence of nodal metastasis, even in the early stages, leading to poor prognosis. For progression and metastasis of cancers, the dominant element considered is cell motility. Fascin, an actin-binding protein has emerged as a protein of general importance for a diverse set of cell protrusions with functions in cell adhesion, cell interactions, and cell migration. The role of Fascin in various carcinomas, including aggressive behaviour in OSCC has been documented, but its role as a key regulator in lymph nodes metastasis is yet to be validated.

Aim: This study was piloted to evaluate and correlate Fascin expression in OSCC lymph nodes and understand the role of Fascin in contemptuous Lesional tissue, as a predictor of survival. A retrospective study designed with 40 archival OSCC cases was included as sample, 20 each of both lymph node metastasis +ve (Group 1) and -ve (Group 2) groups. All the participants were smokeless tobacco user and had tumor located at gingivo-buccal complex.

Results: We established that Fascin over-expression in lymph nodes were significantly associated with clinico-histopathological parameters like staging (p=0.01), tumor size (cT) (p=0.03) and differentiation; and furthermore it was highly significant in correlation to nodal status (cN) (*p≤0.001). Fascin over-expression in lymph node metastasis positive cases correlated with that of Fascin expression in contemptuous Lesional tissue signifying its role in promoting aggressive progression and metastasis. This association was found to be statistically significant (p value=0.05). Overall Survival Analysis of both lymph node metastasis +ve and -ve groups assessed by Kaplan-Meier analysis (taking death and recurrence into consideration) showed patients with high Fascin expression (in lymph node and Lesional tissue) had shorter overall survival than patients who had no to weak Fascin expression.

Conclusion: Our findings thereby establish Fascin expression as a regulator of metastasis in OSCC tumor microenvironment and predictor of survival.