DNA repair and replication proteins as prognostic markers in melanoma

Abstract

Elevated expression of DNA repair and replication genes has been reported in thick, non-fixed primary melanomas that subsequently went on to metastasize, when compared to non-recurrent primary tumours. This increased expression could contribute to the extreme resistance shown by melanoma to DNA-damaging chemotherapeutics. We have investigated the hypothesis that levels of key DNA repair and replication proteins are prognostic biomarkers in melanoma. We used a tissue microarray containing samples from all stages of melanomagenesis to investigate the hypothesis that levels of key DNA repair and replication proteins are prognostic biomarkers in a larger, more representative and readily available set of fixed primary melanomas. High expression of topoisomerase IIα (TOP2A), that relieves torsional stress during DNA replication, and XRCC5 (Ku80), required for DNA double-strand break repair, were associated with significantly worse survival. Two (XRCC5 and TOP2A) of seven DNA repair and replication proteins studied were prognostic for melanoma.