Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites

In B-cell lymphomas, loss of human leukocyte antigen (HLA) class I and II m olecules might contribute to immune escape from CD8(+) and CD4(+) cytotoxic T cells, especially because B cells can present their own idiotype, Loss o f HLA expression and the possible underlying genomic alterations were studi ed in 28 testicular, 11 central nervous system, and 21 nodal diffuse large B-cell lymphomas (DLCLs), the first two sites are considered as immune-priv ileged sites. The analysis included immunohistochemistry, loss of heterozyg osity analysis, and fluorescent in situ hybridization (FISH) on interphase cells and isolated DNA fibers, Total loss of HLA-A expression was found in 60% of the extranodal cases and in 10% of the nodal cases (P < .01), wherea s loss of HLA-DR expression was found in 56% and 5%, respectively (P < .01) , This was accompanied by extensive loss of heterozygosity within the HLA r egion in the extranodal DLCLs, In 3 cases, retention of heterozygosity for D6S1666 in the class II region suggested a homozygous deletion. This findin g was confirmed by interphase FISH that showed homozygous deletions in the class II genes in 11 of the 18 extranodal lymphomas but in none of the 7 no dal DLCLs (P < .001). Mapping by fiber FISH showed variable deletions that always included HLA-DQ and HLA-DR genes. Hemizygous deletions and mitotic r ecombinations often involving all HLA genes were found in 13 of 18 extranod al and 2 of 7 nodal lymphomas. In conclusion, a structural loss of HLA clas s I and II expression might help the B-cell lymphoma cells to escape from i mmune attack. (C) 2000 by The American Society of Hematology.