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Blood, 15 November 2000, Vol. 96, No. 10, pp. 3569-3577
NEOPLASIA
Extensive genetic alterations of the HLA region,
including homozygous deletions of HLA class
II genes in B-cell lymphomas arising in
immune-privileged sites
Sietske A. Riemersma,
Ekaterina S. Jordanova,
Roelandt F. J. Schop,
Katja Philippo,
Leendert H. J. Looijenga,
Ed Schuuring, and
Philip M. Kluin
From the Department of Pathology, Leiden University
Medical Center, Leiden, The Netherlands; Department of
Pathology, Laboratory for Experimental Patho-Oncology, Josephine
Nefkens Institute, University Hospital Rotterdam, The
Netherlands.
In B-cell lymphomas, loss of human leukocyte antigen (HLA)
class I and II molecules might contribute to immune escape from CD8+ and CD4+ cytotoxic T cells, especially
because B cells can present their own idiotype. Loss of HLA expression
and the possible underlying genomic alterations were studied in 28 testicular, 11 central nervous system, and 21 nodal diffuse large
B-cell lymphomas (DLCLs), the first two sites are considered as
immune-privileged sites. The analysis included immunohistochemistry,
loss of heterozygosity 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), whereas 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
region in the extranodal DLCLs. In 3 cases, retention of heterozygosity
for D6S1666 in the class II region suggested a homozygous deletion.
This finding 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 nodal DLCLs (P < .001). Mapping by
fiber FISH showed variable deletions that always included HLA-DQ and
HLA-DR genes. Hemizygous deletions and mitotic recombinations often
involving all HLA genes were found in 13 of 18 extranodal and 2 of 7 nodal lymphomas. In conclusion, a structural loss of HLA class I and II
expression might help the B-cell lymphoma cells to escape from immune attack.
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