Genetic heterogeneity in adjacent normal mucosa of oral squamous cell carcinoma is a marker of poor prognosis

Background & Objectives: Intra-tumoural heterogeneity (ITH) displayed by tumour cells represents a diagnostic challenge when assessing tumour mutational profile aimed to the delivery of effective targeted therapies. In Oral Squamous cell carcinoma (OSCC), ITH has been reported both in tumour cells and in related adjacent mucosa. The presence of genetic heterogeneity in the adjacent mucosa can be interpreted as evidence of the field cancerization phenomenon (field het- erogeneity, FH). Aim of this study was to investigate the clinical impact of ITH and FH on loco regional control. Methods: Ten OSCC patients who received radical surgery and staged T2-T4 (5 recurrent and 5 non-recurrent) were enrolled in this study. Multiple areas were sampled from the bulk of the tumour and the adjacent non-neoplastic mucosa. NGS mutational analysis of 10 OSCC driver genes were investigated and used to calculate ITH and FH among differ- ent area of the tumour. Results: Mutational analysis highlighted that a single sample is often scarcely accurate in assessing genetic profiles of tumours. High values of ITH were found in both groups with a tendency to be higher in recur- rent OSCC (p=0,095). Interestingly, the FH was found significantly lower in the non-recurrent OSCC group (p=0,032).