DNA repair and replication proteins as prognostic markers in melanoma

Aims: Elevated expression of DNA repair and replicationgenes has been reported in thick, non-fixed primarymelanomas that subsequently went on to metastasize,when compared to non-recurrent primary tumours.This increased expression could contribute to theextreme resistance shown by melanoma to DNA-dam-aging chemotherapeutics. We have investigated thehypothesis that levels of key DNA repair and replicationproteins are prognostic biomarkers in melanoma.Methods and results: We used a tissue microarraycontaining samples from all stages of melanomagenesisto investigate the hypothesis that levels of key DNArepair and replication proteins are prognostic biomar-kers in a larger, more representative and readilyavailable set of fixed primary melanomas. High expres-sion of topoisomerase IIa (TOP2A), that relievestorsional stress during DNA replication, and XRCC5(Ku80), required for DNA double-strand break repair,were associated with significantly worse survival.Conclusions: Two (XRCC5 and TOP2A) of seven DNArepair and replication proteins studied were prognosticfor melanoma.Keywords: chemotherapy, ERCC1, melanomagenesis, topoisomerase IIa, XRCC5