Biology of metastatic disease

Purpose Despite successful treatment of the primary tumour, uveal melanoma (UM) disseminates haematogeneously in approx. 50% of patients, usually to the liver. In a few patients, metastases can be treated surgically; however, in the majority, there is no effective chemotherapy, as the “magic bullet” for metastatic UM has yet to be found. Methods Literature review to provide an overview of the morphological, immunohistochemical and molecular genetic features of metastatic UM. In addition, immunohistochemical studies for various proteins, including BRCA1 associated protein 1 (BAP‐1), were performed on tissue microarrays of matched primary and metastatic UM. The percentage of tumor cell positivity was scored blind by independent assessors, and correlations were measured with statistical tests. Results Literature review revealed only a few studies of human UM metastases, including some on fine needle aspiration biopsies, liver resections, or on autopsy material. Occasional studies examined matched primary and metastatic tumour samples. The majority of investigations had performed immunohistochemistry, with only a few examining the genetic changes of these tumours. The results of our analyses of a cohort comprising >100 metastatic UM will be presented. We confirm that absence of BAP1 correlates with metastasis of UM; however, metastasis can occur despite BAP1 expression. Conclusion In order to understand the dissemination process of UM, including the mechanisms involved in successful tumour cell colonisation, the tumour microenvironment‐, the immunophenotype‐, genotype and possible susceptible signalling pathways of the melanoma cells, it is essential that greater efforts are made to access and investigate these samples. Only in this way can treatment of the systemic phase of UM be successful.