Circulating Melanoma Cells

Abstract

Cutaneous Melanoma is an aggressive cancer which accounts for 80% of skin cancer deaths. Australia has the highest incidence world-wide and rates are increasing annually (10,000 new cases and 1,700 deaths per year). Notably it is the most common cancer in 15-39 year olds and the leading cancer related cause of death in young males (WA Cancer Registry 2007). In the USA, incidence is rising faster than other cancers, with 60,000 new cases and 8,000 deaths in 2007 1. Mortality rates remain high due to metastasis of the tumour. Once melanoma has metastasised, survival is commonly 6 to 9 months, with 5-year survival rate less than 40% 2-4. Several prognostic factors have been identified, based upon pathological evaluation of the primary tumour 5 and lymph node metastases 6. However, metastatic disease particularly micrometastasis, is difficult to detect and occurs in over 30% of patients, including 8-30% of patients with in situ melanoma 7-9 and 15% of patients whose lymph nodes are negative at the time of surgical intervention 10,11. In addition, metastasis can occur up to 35 years after diagnosis 12. Effective therapies providing long term survival are very limited (<20%), often due to drug resistance associated with prevailing undetected mutations or acquisition of new mutations. Surprisingly few studies 13-15 have monitored circulating cells as a means of determining disease progression, and/or treatment efficacy or for design of personalised treatment strategies. A great deal of information has been compiled in an attempt to identify prognostic factors that correlate with clinical outcomes. Current clinical staging is performed using measures of the pathological features of the primary tumour, lymph node and distant metastases 6, as well as LDH levels and now also, genetic changes in the primary tumour 16-19. The inability to accurately predict melanoma progression, may be related to the fact that the majority of studies use primary and less often, metastatic tumour tissue to stratify patients and delineate prognostic markers. Very few studies analyse the circulating tumour cell (CTC) phenotype that gives rise to the metastases. There is therefore an unmet need for detailed analyses of CTCs to provide early identification of metastatic risk and prognosis and evaluation of adjuvant therapies. 2.