||The aim of this PhD project is to validate initial exploratory data and determine important molecular events in the development extracapsular spread (ECS), the most biologically aggressive metastatic phenotype in oral squamous cell carcinoma (OSCC). Our hypothesis is that molecular events in key pathways from primary site tissue are associated with this aggressive metastatic phenotype. The focus will be on the detailed analysis of data obtained from microarray techniques. These have identified an 8-gene signature for ECS with 78% sensitivity & 86% specificity. Power analysis showed that 90% of all = twofold differences in gene expression between node negative & ECS cases were significant. Affected pathways are implicated in invasion and metastasis. Analysis will include validation of these findings using single gene assays, immunohistochemistry using tissue microarrays and functional studies investigating motility and invasion through organotypic modelling. The subsequent clinical value of this will be to understand the underlying biological mechanisms with potential for biomarker discovery in ECS.