Expression of transporters associated with antigen processing and human leucocyte antigen class I in malignant melanoma and its association with prognostic factors

Abstract

Background: Low expression of transporters associated with antigen processing (TAP) and human leucocyte antigen (HLA) class I, due to defects in the antigen presentation pathway, is frequently found in human tumours, including malignant melanoma (MM). This immune evasion renders many tumours unrecognizable by the host immune surveillance system and appears to play a role in the clinical course of the tumour, probably because it provides tumour cells with a mechanism to escape cytotoxic T-lymphocyte recognition and destruction. However, the histopathological significance of TAP and HLA class I antigen defects in MM remains unclear.

Objective: To study the expression of TAP and HLA class I antigen in MM and the relationship between them. To investigate the correlation between histopathological characteristics and expression of these molecules in MM.

Methods: Tissue sections from 77 patients with MM and 20 with naevi were examined using immunohistochemistry and morphological quantitative analysis for protein expression of TAP1, TAP2 and HLA class I antigen.

Results: Positive TAP1, TAP2 and HLA class I antigen immunostaining was observed in 23%, 12% and 64% of MM lesions, respectively, and the expression of HLA class I was positively correlated with that of TAP1 and TAP2. However, expression of these molecules was positive in all of the pigmented naevi lesions. Reduced TAP1 and TAP2 protein expression in melanoma lesions was significantly associated with invasive growth, Clark's level and tumour-infiltrating lymphocytes. Reduced HLA class I antigen protein expression was only associated with tumour-infiltrating lymphocytes.

Conclusions: Our data suggest that reduced TAP1, TAP2 and HLA class I antigen protein expression in MM may contribute to the immune escape phenotype of human melanoma cells, and the main cause of reduced HLA class I expression may be the decreased TAP1 and TAP2 levels.