17. Expression of cancer testis antigens (CTAg) is prognostic in stage III melanoma

Abstract

Background Patients with advanced (AJCC Stage III/IV) malignant melanoma (MM) have variable outcomes. Immunological mechanisms may be important in disease progression and in developing future therapies. CTAgs are immunogenic molecules expressed in normal testis and some cancers. While CTAg function is unknown, expression confers poorer progression free survival (PFS) but not overall survival (OS) in patients with Stage II MM (Svobodova et al. 2011). Here we investigate stage III/IV patients to determine prognostic impact of CTAg expression in advanced MM and correlate with subsets of tumour infiltrating lymphocytes (TILs). Methods TMAs created from formalin fixed, paraffin embedded (FFPE) tumours of patients with late stage (62 stage III, 94 stage IV) MM were stained for the following CTAgs: MAGE-A1, MAGE-A3/4, NY-ESO-1, GAGE, SAGE1, NXF2/CT39, ACTL8/CT57, MAGEC1/CT7, MAGEC2/CT10 and CT45. TILs were characterised by CD8, CD4 and FoxP3 immunohistochemical staining. Correlation with clinico-histopathological factors was tested using Fisher’s exact tests. Kaplan-Meier curves were used to plot survival curves. Results Frequencies of CTAg expression were similar between stage III and IV disease. In stage III tumours, CTAg expression was significantly associated with improved PFS (median 69 vs 17 months, p = 0.02), and OS (100 vs 46 months, p = 0.038). A high CD8:Treg ratio was also associated with improved PFS (82 vs 21 months). The associations were not seen in stage IV MM. Conclusions In contrast to previous findings in stage II MM, CTAg expression was associated with improved PFS and OS in stage III disease. As a high CD8:Treg ratio also conferred better outcome, the possible impact of emergent spontaneous immunity against CTAg warrants further investigation in patients with advanced MM.