Angiogenesis is a crucial aspect of tumor progression and metastases.  Angiogenesis and extracellular matrix (ECM) proteins are highly expressed in many cancers and serum levels of these markers are elevated in thyroid cancer patients.  Anti-angiogenic strategies have been highly successful in preclinical models of thyroid cancer including the most aggressive anaplastic phenotype.  Our long term goal is to develop effective adjuvant therapy for advanced (recurrent or metastatic) and anaplastic thyroid cancer.  Our preliminary results from thyroid cancer cell lines suggest that anaplastic thyroid cancer expresses more angiogenesis and extra-cellular matrix genes at higher levels.  Therefore, we have chosen to examine the genetic profile of advanced thyroid cancer, paying particular attention to expression patterns of angiogenesis and ECM - related genes in an attempt to identify patients at risk for metastasis and poor outcome.  Ras and Raf pathways appear to be targets for therapeutic manipulation in thyroid cancer, because thyroid cancers are unique in harboring mutations of all three isoforms of the oncogenic Ras, and many anaplastic thyroid cancers have Raf mutations.