M. Feenstra et al., HLA class I expression and chromosomal deletions at 6p and 15q in head andneck squamous cell carcinomas, TISSUE ANTI, 54(3), 1999, pp. 235-245
Loss at the chromosomal region 6p21.3 is a frequent event in head and neck
squamous cell carcinomas (HNSCC). Since the human leukocyte antigen (HLA) c
omplex is located at 6p21.3, loss of heterozygosity (LOH) of this region ma
y provide tumour cells with an immune-escape tumour phenotype, In the prese
nt study, we have studied the correlation of HLA class I, TAP1 and TAP2 exp
ression and LOH at 6p21.3. HLA class I and TAP1 and TAPE protein expression
was analysed by immunohistochemical procedures, A panel of 41 HNSCC with d
ownregulated HLA class I expression was selected for LOH studies using 5 mi
crosatellite markers located at 6p21.3 (D6S105, D6S265, D6S276, D6S273, D6S
291) and 2 markers located at the chromosome 6 centromere (D6S473) and the
6p telomere (D6S277). In addition, LOH of the beta-2-microglobulin (beta(2)
m) gene was studied using 2 microsatellite markers flanking the beta(2)m ge
ne (D15S126 and D15S153) and was correlated with beta(2)m and HLA class I e
xpression. In 20/41 (49%) of the HNSCC, allelic loss for at least one locus
at 6p21.3 was found. Loss at 15q was found in 4/10 (40%) HNSCC with downre
gulated beta(2)m expression and in 12/41 (29%) HNSCC with downregulated HLA
class I expression. Our data show that downregulation of HLA class I expre
ssion is correlated with loss of chromosomal regions at 6p21.3 in HNSCC, In
addition, LOH at 6p21.3 and 15q in 10 paired samples of DNA. derived from
the primary HNSCC, the lymph node metastases and from peripheral blood lymp
hocytes (PBLs) was studied. Five (5/10) primary tumours contained the same
deletion as the corresponding lymph node metastases. The other cases contai
ned deletions either in the primary tumour (3 cases) or in the lymph node m
etastases (1 case) or no deletions at all (1 case).