Major histocompatibility antigens and antigen-processing molecules in uveal melanoma

Malignant transformation of cells is frequently associated with abnormalities in the human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLA antigens mediate interactions of tumor cells with T cells and natural killer cells. Uveal melanoma is a highly malignant tumor of the eye and is characterized by hematogenic spread to liver. Antigen-processing molecules (APMs) are necessary for efficient expression of HLA class I antigens. We studied the expression of HLA antigens and the APM in uveal melanomas by immunohistochemistry and correlated clinicopathologically.

HLA class I antigen, beta(2)-microglobulin (beta(2)-m), HLA class II antigens, and the APM comprising proteasomal subunits low molecular mass polypeptide (LMP) 2, beta-subunit of LMP2-Delta, LMP 10, transporter associated protein 1 subunit, and chaperone molecules tapasin and calnexin were studied in 41 primary uveal melanoma archival specimens by immunohistochemistry. Immunoanalysis was done by a semiquantitative method and correlated with extrascleral extension, cell types, and the largest tumor diameter.

HLA class I antigen, beta(2)-m, HLA class II antigen, and the APM were decreased (negative staining in 29 tumors and dull staining in 3 tumors) in 100% (32 of 32) uveal melanomas with no extrascleral extension. (P = 0.01) and positive (bright staining) in 67% (4 of 9) tumors with liver metastasis. Decreased immunoexpression of HLA antigens and the APM was seen in nonepithelioid cell melanomas. There was no correlation with largest tumor diameter.

Our data suggest decreased expression of HLA, and APM are seen in uveal melanomas with no extrascleral extension and in nonepithelioid cell melanomas. Decreased expression of APM may contribute to decreased HLA class I antigen expression.