Because changes in the expression level of antigen-processing machinery (APM) components and HLA class I and II
antigens in
melanoma cells are expected to affect their interactions with the immune system of the host, we assessed the clinical relevance of quantitative variations in the expression of these molecules in
melanoma lesions. Short-term (<10 in vitro passages)
melanoma cell lines isolated from 85 American Joint Committee on
Cancer (AJCC) stage III and IV patients were stained with APM component and HLA
class I antigen-specific and HLA
class II antigen-specific
monoclonal antibodies and analyzed by flow cytometry. The phenotype of all
tumors was characterized by intertumor and intratumor heterogeneity in the expression of all the markers and by significant correlations in the level of expression of markers belonging to the HLA
class I antigen-processing and presentation pathway. Hierarchical clustering of the mean fluorescence intensity data defined two main clusters of
tumors. The corresponding groups of patients differed significantly in the overall survival but not in other relevant clinical variables, including AJCC stage and
therapy received after surgery. Cox regression analysis showed that beta2-microglobulin and HLA
class II antigen expression were significantly associated with patients' survival. This evidence was corroborated by the immunohistochemical analysis for HLA
class II antigen expression of
melanoma lesions from an unrelated group of 52 AJCC stage III and IV patients. These results suggest that quantitative variations in APM component and HLA expression in
melanoma lesions from AJCC stage III and IV patients may have an effect on the
clinical course of the disease.