Immunohistochemical analysis of the expression of MAGE-A and NY-ESO-1 cancer/testis antigens in diffuse large B-cell testicular lymphoma

Abstract

Background: Primary testicular lymphoma (PTL) is a rare and lethal disease. The most common histological subtype is diffuse large B-cell lymphoma (DLBCL). Standard treatments are frequently ineffective. Thus, the development of novel forms of therapy is urgently required. Specific immunotherapy generating immune responses directed against antigen predominantly expressed by cancer cells such as cancer-testis antigens (CTA) may provide a valid alternative treatment for patients bearing PTL, alone or in combination with current therapies.

Methods: Three monoclonal antibodies (mAbs), 77B recognizing MAGE-A1, 57B recognizing an epitope shared by multiple MAGE-A CTA (multi-MAGE-A specific) and D8.38 recognizing NY-ESO-1/LAGE-1 were used for immunohistochemical staining of 27 PTL, including 24 DLBCL.

Results: Expression of MAGE-A1 was infrequently detectable in DLBCL specimens (12.50%), whereas multi-MAGE-A and NY-ESO-1/LAGE-1 specific reagents stained the cytoplasms of tumor cells in DLBCL specimens with higher frequencies (54.17% and 37.50%, respectively) with different expression levels.

Conclusions: These results suggest that MAGE-A and NY-ESO-1/LAGE-1, possibly in combination with other CTA, might be used as targets for specific immunotherapy in DLBCL.

Figure 1

Immunohistochemical detection of MAGE-A1, multi-MAGE-A, and NY-ESO-1/LAGE-1 in diffuse large B-cell lymphoma tissues. DLBCL tissues were stained either with MAGE-A1 specific mAb 77B (A.), or multi-MAGE-A specific mAb 57B (B.) or with NY-ESO-1/LAGE-1 specific mAb D8.38 (C.). Representative staining displaying positivity for these CTA are shown.

Figure 2

Percentages of DLBCL samples showing evidence of positive staining upon incubation with CTA specific mAbs. Testis sections from DLBCL tissues were stained, as described in materials and methods, by IHC with 77B, 57b and D8.38 CTA specific mAbs. DLBCL samples were categorized by taking into account the number of positive reactions per tissue.