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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.