Expression of cancer testis antigen CT45 in classical Hodgkin lymphoma and other B-cell lymphomas

Abstract

We have shown previously that cancer/testis (CT) antigen, CT45, is expressed in various epithelial cancers at a frequency of <5% to approximately 35%. In this study, the protein expression of CT45 was examined in non-Hodgkin B-cell lymphomas and classical Hodgkin lymphoma by immunohistochemical analysis. Serological response to CT45 was also evaluated by ELISA using CT45 recombinant protein and sera from patients with Hodgkin lymphoma. None of the 80 low-grade B-cell lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma, expressed CT45. In comparison, CT45 was expressed in 28 of 126 (22%) diffuse large B-cell lymphomas (DLBCL). A remarkably high percentage (42/72, 58%) of classical Hodgkin lymphoma contained CT45-positive Reed-Sternberg cells. Nodular sclerosis and mixed-cellularity subtypes had similar frequency of CT45 expression, but most EBV-positive cases were CT45 negative. Gray-zone lymphoma (cases with features of both DLBCL and classical Hodgkin lymphoma) also showed frequent (64%) CT45 expression. Evaluation of reactive lymphoid tissues showed scattered CT45-positive lymphocytes in a single case of florid follicular hyperplasia, raising the possibility that this case was an evolving malignancy. Despite frequent CT45 expression, only 1 of 67 Hodgkin lymphoma patients had detectable anti-CT45 antibodies in the serum, suggesting that the immune response to CT45 may be suppressed. In conclusion, classical Hodgkin lymphoma has the highest frequency of CT45 expression among all malignancies tested to date, the frequency of CT45 expression in DLBCL is similar to that seen in epithelial cancers, and low-grade non-Hodgkin B-cell lymphomas do not express CT45.

Fig. 1.

Expression of CT proteins in various types of lymphoma (A–H). (A and B) CT45 expression in diffuse large B-cell lymphoma. (A) Two thirds of the positive cases showed diffuse strong nuclear staining. (B) The remaining cases showed weaker, and often focal, staining pattern. Nonneoplastic small lymphocytes are negative. (C–F) Expression of CT45 in cHL lymphoma, in comparison with MAGE-A and NY-ESO-1. (C) Most CT45-positive Hodgkin lymphomas showed diffuse nuclear staining of RS cells and variants in moderate to strong intensity (Inset shows an RS cell). (D) Weaker staining was seen in the remaining cases. (E) Expression of MAGE-A was detected in only 1 of 25 cases examined, showing a mixed nuclear and cytoplasmic expression pattern. (F) Similarly, expression of NY-ESO-1 was seen in only one case, as a weak to moderate cytoplasmic staining. (G and H) Expression of CT45 in gray zone lymphoma. (G) Large anaplastic tumor cells with prominent nucleoli are seen in a background of small lymphocytes and abundant eosinophils, similar to that seen in cHL. (H) The tumor cells were diffusely strongly positive for CT45 as well as for B-cell surface marker CD20 (Inset). (Scale bars, 100 μm.)

Fig. 2.

CT45-positive cells in a lymph node with florid follicular hyperplasia. (A) Large, irregularly shaped follicles were prominent. (B) Scattered intermediate to large lymphoid cells with vesicular nuclei were noted in the follicles and in the interfollicular areas. (C and Inset) Some of these cells probably correspond to CT45-positive cells. (Scale bars, 100 μm.)