Human leukocyte antigen class I expression. Marker of poor prognosis in uveal melanoma.
OBJECTIVE
Because the expression of human leukocyte antigen (HLA) antigens is important for immunologic recognition of tumor cells, we determined expression of locus-specific HLA class I antigens in uveal melanoma and tested whether the level of HLA expression was related to prognosis or associated with known prognostic parameters.


METHODS
Expression of HLA-A and -B antigens was determined on 30 formalin-fixed and paraffin-embedded sections of uveal melanoma by immunohistochemistry with locus-specific monoclonal antibodies and scored semiquantitatively.


RESULTS
The level of expression of HLA-A and -B varied between uveal melanomas. Expression levels of HLA-A and -B were significantly correlated (P = 0.02). High HLA-B expression was significantly correlated with the presence of epithelioid cells (P = 0.04) in the tumor. Expression levels of HLA-A as well as of HLA-B, cell type, mitotic rate, Mib-1 score, and largest tumor diameter were significant predictive factors for survival. High expression of HLA-A and -B was associated with a decreased survival. Multiple Cox regression analysis with stepwise selection of covariates showed that the contribution of HLA-A expression to survival (P = 0.0003) exceeded that of tumor diameter (P = 0.02) and Mib-1 score (P = 0.04).


CONCLUSIONS
Lack of expression of HLA-A as well as of HLA-B antigens on uveal melanoma is correlated with a better patient survival. Our data suggest that shedding of uveal melanoma micrometastases with a low expression of HLA class I into the systemic circulation may facilitate their removal and prevent the development of metastases. These findings support a protective role for natural killer cells in the development of metastatic disease in uveal melanoma.
Blom
D J
DJ
Department of Ophthalmology, Leiden University Hospital, The Netherlands.
Luyten
G P
GP
Mooy
C
C
Kerkvliet
S
S
Zwinderman
A H
AH
Jager
M J
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D015234:HLA-A Antigens / Q000378:metabolism*; D015235:HLA-B Antigens / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; D015234:HLA-A Antigens; D015235:HLA-B Antigens