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Keywords:

  • antigen-processing molecules;
  • calnexin;
  • cytotoxic T lymphocytes;
  • human leukocyte antigen;
  • immunohistochemistry;
  • retinoblastoma;
  • tapasin

Abstract

BACKGROUND

Malignant transformation of cells is frequently associated with abnormalities in human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLAs mediate interactions of tumor cells with cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Retinoblastoma is the most common intraocular malignant tumor in childhood and is characterized by direct spread to the optic nerve and orbit as well as hematogeneous and lymphatic spread. Little is known about the role of HLA expression in the progression of this malignant disease.

METHODS

HLA Class I antigen, β2-microglobulin (β2-m), HLA Class II antigens, and the antigen-processing molecules (APMs) of the HLA Class I pathway, including proteasomal subunits (low–molecular mass polypeptide 2 [LMP-2] and LMP-10), the transporter-associated protein (TAP-1) subunit, the binding protein tapasin, and the chaperone molecule calnexin, were studied in 30 archival retinoblastoma specimens by immunohistochemistry. Immunoanalysis was performed based on the International Histocompatibility Working Group Project Description.

RESULTS

HLA Class I antigen, β2-m, HLA Class II antigen, and APMs were positive in 12 tumors with no invasion and were decreased in 13 tumors with choroidal and optic nerve invasion. The difference in HLA and APM expression between the 2 groups was statistically significant (P < 0.001).

CONCLUSIONS

Decreased expression of HLA was observed in aggressive tumors and in poorly differentiated tumors. The current findings support a role for both CTLs and NK cell-mediated control of tumor growth in the clinical course of retinoblastoma. Cancer 2004;100:1059–69. © 2004 American Cancer Society.