Selective monomorphic and polymorphic HLA class I antigenic determinant loss in surgically removed melanoma lesions

• Published in: Tissue antigens 2005-05, Vol.65 (5), p.419-428
• Main Authors: Kageshita, T., Ishihara, T., Campoli, M., Ferrone, S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - immunology; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Genes, MHC Class I; HLA class I antigen; HLA-A Antigens - genetics; HLA-A Antigens - immunology; HLA-B Antigens - genetics; HLA-B Antigens - immunology; Humans; immunoselection; immunotherapy; Male; melanoma; Melanoma - genetics; Melanoma - immunology; Melanoma - mortality; Melanoma - pathology; Melanoma - secondary; Melanoma - surgery; Middle Aged; Prognosis; Skin - immunology; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Skin Neoplasms - surgery; Survival Analysis
• ISSN: 0001-2815; 1399-0039
• DOI: 10.1111/j.1399-0039.2005.00381.x

:  The analysis of human leukocyte antigen (HLA) class I allospecificity expression in malignant lesions has been hampered by the limited availability of HLA class I allospecificity‐specific monoclonal antibodies (mAbs) which stain tissues in immunohistochemical (IHC) reactions. During the 12th International Histocompatibility Workshop, the HLA and cancer component made available a panel of mAbs capable of detecting monomorphic, locus‐ and allo‐specific HLA class I antigenic determinants in surgically removed frozen tissue sections by IHC staining. In the present study, we have utilized this panel of mAbs to analyze the expression of HLA class I allospecificities in 33 primary and in 11 metastatic lesions surgically removed from HLA‐typed patients with malignant melanoma, as this information contributes to determine the extent of HLA class I antigen abnormalities in melanoma lesions. HLA class I antigens were downregulated in six (18.2%) of the primary lesions and in six (54.5%) of the metastatic lesions. Selective loss of HLA‐A and HLA‐B antigens was detected in two (6.1%) and in one (3.0%), respectively, of the primary lesions, but in none of the metastases. HLA‐A and HLA‐B antigens were downregulated in three (9.1%) and four (36.4%) of the primary and metastatic lesions, respectively. Selective loss of one or more HLA class I allospecificities was found in 10 (33.0%) and two (18.0%) of the 33 primary and 11 metastatic melanoma lesions analyzed, respectively. HLA class I antigen abnormalities were present in 16 (48.5%) of the 33 primary lesions analyzed (i.e. six lesions demonstrating abnormal reactivity with HLA class I monomorphic‐specific mAb, two lesions demonstrating selective abnormal reactivity with HLA‐B locus‐specific mAb, one lesion demonstrating selective abnormal reactivity with HLA‐A and HLA‐B locus‐specific mAbs, and seven lesions demonstrating selective abnormal reactivity with HLA class I allele‐specific mAb). Furthermore, HLA class I antigen abnormalities were present in nine (81.8%) of the 11 metastatic lesions analyzed (i.e. six lesions demonstrating abnormal reactivity with HLA class I monomorphic‐specific mAb, one lesion demonstrating selective abnormal reactivity with HLA‐A locus‐specific mAb, and two lesions demonstrating selective abnormal reactivity with HLA class I allele‐specific mAb). It cannot be ruled out that the frequency of HLA class I allospecificity abnormalities is higher, as the expression of several HLA class I allos