Jr. Grandis et al., Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: Clinical and immunogenetic consequences, CLIN CANC R, 6(7), 2000, pp. 2794-2802
The expression of human leukocyte antigen (HLA) class I molecules on the ce
ll surface is necessary for the presentation of peptide antigens to cytotox
ic CD8+ T lymphocytes of the immune system. Down-regulation of HLA class I
gene expression has been implicated in tumorigenesis, including squamous ce
ll carcinoma of the head and neck (SCCHN), Loss of MHC class I antigens may
be one mechanism by which tumor cells escape immune detection, We performe
d prospective immunostaining of 26 primary SCCHN tumors and samples of norm
al mucosa harvested several centimeters away from the primary tumor, using
a large panel of antibodies directed against allele-specific as well as mon
omorphic determinants of HLA class I molecules. Loss of expression of HLA c
lass I proteins in the tumor was found in 50% (13 of 26) of primary tumors
and was highly correlated with HLA loss in the corresponding normal mucosa
(P < 0.0001), Further analysis demonstrated that the loss of HLA class I ex
pression in the tumor was significantly associated with regional lymph node
metastases (nodal stage; P = 0.0388), and that the number of HLA class I a
lleles lost in the normal mucosa was associated with subsequent development
of a new primary aerodigestive tract cancer (P = 0.042), A patient with tw
o metachronous cancers available for analysis had no evidence of HLA loss i
n the first tumor, demonstrated allelic loss in the second cancer, and subs
equently died of disease. These results suggest that the loss of expression
of HLA class I alleles may have prognostic implications.