1485

CTAG1B

CT6.1|CTAG|CTAG1|CTAG1A|ESO1|LAGE-2|LAGE2B|NY-ESO-1;cancer/testis antigen 1B;CTAG1B;cancer/testis antigen 1B

New York esophageal squamous cell carcinoma 1|autoimmunogenic cancer/testis antigen NY-ESO-1|cancer antigen 3|cancer/testis antigen 1|cancer/testis antigen 6.1|l antigen family member 2

Xq28

protein-coding

BACKGROUND: Neuroblastoma is the most common solid extracranial tumor in childhood, still with poor survival rates for metastatic disease. Neuroblastoma cells are of neuroectodermal origin and express a number of cancer germline (CG)antigens. These CG antigens may represent a potential target for immunotherapy such as peptide-based vaccination strategies. OBJECTIVE: The purpose of this study was to analyze the presence of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 on an mRNA and protein level and to determine the expression of MHC class I and MHC class II antigens within the same tumor specimens. METHODS: A total of 68 tumors were available for RT-PCR, and 19/68 tumors were available for immunohistochemical (IHC) analysis of MAGE-A1, MAGE-A3/A6, and NY-ESO-1. In parallel, the same tumors were stained with a panel of antibodies for MHC class I and MHC class II molecules. RESULTS: Screening of 68 tumor specimens by RT-PCR revealed expression of MAGE-A1 in 44%, MAGE-A3/A6 in 21%, and NY-ESO-1 in 28% of cases. Immunohistochemistry for CG antigens of selected tumors showed good agreement between protein and gene expression. However, staining revealed a heterogeneous expression of CG antigens. None of the selected tumors showed MHC class I or MHCclass II expression. CONCLUSIONS: mRNA expression of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 is congruent with the protein expression as determined by immunohistochemistry. The heterogeneous CG-antigen expression and the lack of MHC class I and II molecules may have implications for T-cell-mediated immunotherapyin neuroblastoma.

BACKGROUND: NY-ESO-1 is a human gene that codes for antigens that are expressed in malignancies of various histological types, but not in normal tissues, exceptthe testes. The expression of NY-ESO-1 in intracranial brain tumors including astrocytomas (ASTRs) and medulloblastomas (MEDs)/primitive neuroectodermal tumors (PNETs) was examined since the expression of NY-ESO-1 has only previously been explored in depth in neuroblastomas. MATERIALS AND METHODS: During our immunohistochemical study, a sensitive, four-step, alkaline phosphatase-conjugated antigen detection technique was employed. The expression of NY-ESO-1 was thereby examined in 6 cases of MED/PNET and 14 cases of ASTR. RESULTS: ALL 6 MED/PNET cases demonstrated high levels of immunoreactivity (overexpression) with the highest immunostaining intensity grades A and B. In the astrocytic tumors of various subtypes examined, the level of NY-ESO-1 expressionwas not as strong as that in MEDs/PNETs. However, there was a significant increase in expression level when comparing low-grade pilocytic ASTRs to high-grade anaplastic ASTRs and glioblastomas. CONCLUSION: As evidenced by our results, NY-ESO-1 overexpression increases as the malignancy grade of the astrocytic tumors increases. These data suggest that antigen-directed immunotherapy of primary brain tumors could target cancer/testis antigens (CTAs), especially those expressed at higher frequency such as NY-ESO-1.

cancer-germline genes (CGGs) code for immunogenic antigens that are present in various human tumors and can be targeted by immunotherapy. Their expression has been studied in a wide range of human tumors in adults. We measured the expression of 12 CGGs in pediatric brain tumors, to identify targets for therapeutic cancer vaccines. Real Time PCR was used to quantify the expression of genes MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MAGE-C2, NY-ESO-1 and GAGE-1,2,8 in 50 pediatric brain tumors of different histological subtypes. Protein expression was examined with immunohistochemistry. Fifty-five percent of the medulloblastomas (n = 11), 86% of the ependymomas (n = 7), 40% ofthe choroid plexus tumors (n = 5) and 67% of astrocytic tumors (n = 27) expressed one or more CGGs. Immunohistochemical analysis confirmed qPCR results. With exception of a minority of tumors, the overall level of CGG expression in pediatric brain tumors was low. We observed a high expression of at least one CGG in 32% of the samples. CGG-encoded antigens are therefore suitable targets in a very selected group of pediatric patients with a brain tumor. Interestingly, glioblastomas from adult patients expressed CGGs more often and at significantlyhigher levels compared to pediatric glioblastomas. This observation is in line with the notion that pediatric and adult glioblastomas develop along different genetic pathways.