PMID- 10914726 OWN - NLM STAT- MEDLINE DCOM- 20001116 LR - 20220408 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 6 IP - 7 DP - 2000 Jul TI - Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: clinical and immunogenetic consequences. PG - 2794-802 AB - The expression of human leukocyte antigen (HLA) class I molecules on the cell surface is necessary for the presentation of peptide antigens to cytotoxic CD8+ T lymphocytes of the immune system. Down-regulation of HLA class I gene expression has been implicated in tumorigenesis, including squamous cell 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 performed prospective immunostaining of 26 primary SCCHN tumors and samples of normal mucosa harvested several centimeters away from the primary tumor, using a large panel of antibodies directed against allele-specific as well as monomorphic determinants of HLA class I molecules. Loss of expression of HLA class 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 expression in the tumor was significantly associated with regional lymph node metastases (nodal stage; P = 0.0388), and that the number of HLA class I alleles lost in the normal mucosa was associated with subsequent development of a new primary aerodigestive tract cancer (P = 0.042). A patient with two metachronous cancers available for analysis had no evidence of HLA loss in the first tumor, demonstrated allelic loss in the second cancer, and subsequently died of disease. These results suggest that the loss of expression of HLA class I alleles may have prognostic implications. FAU - Grandis, J R AU - Grandis JR AD - Department of Otolaryngology and Pharmacology, University of Pittsburgh, Pennsylvania 15213, USA. FAU - Falkner, D M AU - Falkner DM FAU - Melhem, M F AU - Melhem MF FAU - Gooding, W E AU - Gooding WE FAU - Drenning, S D AU - Drenning SD FAU - Morel, P A AU - Morel PA LA - eng PT - Journal Article PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Alleles MH - Carcinoma, Squamous Cell/*genetics/immunology/pathology/therapy MH - Combined Modality Therapy MH - Female MH - *Genes, MHC Class I MH - Haplotypes MH - Head and Neck Neoplasms/*genetics/immunology/pathology/therapy MH - Histocompatibility Antigens Class I/*analysis/genetics MH - Histocompatibility Testing MH - Humans MH - *Loss of Heterozygosity MH - Male MH - Middle Aged MH - Mucous Membrane/immunology/pathology MH - Neoplasm Staging EDAT- 2000/07/29 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/07/29 11:00 PHST- 2000/07/29 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/07/29 11:00 [entrez] PST - ppublish SO - Clin Cancer Res. 2000 Jul;6(7):2794-802.