Decreased HLA-A expression in prostate cancer is associated with normal allele dosage in the majority of cases.
A comparison has been made of the phenotypic expression of MHC class I antigens with the corresponding HLA-A genotype in 15 cases of benign prostatic hyperplasia (BPH) and 34 cases of primary locally invasive prostatic carcinoma. Expression of class 1 protein, detected by immunocytochemistry, was partially or completely lost in approximately 90% of the tumours examined. Comparative genomic analysis of the beta2 microglobulin (beta2m) gene and 15 individual HLA-A haplotypes using a polymerase chain reaction (PCR)-based method demonstrated abnormal gene dosage in the minority of cases: homozygous deletion of the beta2m locus was detected in one case and HLA-A allele in two cases (HLA-A1 and HLA-A2, respectively), representing approximately 8% of the population studied. This first comparative study of gene dosage and expression of class 1 protein reported for prostate cancer reveals that deletion is not the cause of the partial or complete loss seen in the majority of cases. This raises the possibility, in the future, for novel selective immunomodulatory therapeutic strategies which stimulate a clinically significant re-expression of class 1 protein and associated cytotoxic T-cell response.
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Department of Histopathology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Abel
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Mitchell
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Foster
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Lalani
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D000483:Alleles; D046508:Culture Techniques; D018628:Gene Dosage; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism
D015234:HLA-A Antigens; D009363:Neoplasm Proteins; D001613:beta 2-Microglobulin