Cancer-testis (CT) antigen expression in medulloblastoma.
Medulloblastoma is the most common childhood malignant tumor of the central nervous system. Treatment of medulloblastoma requires harmful therapy and nevertheless carries a poor prognosis. Due to their presence in various cancers and their limited expression in normal tissues, CT antigens are ideal vaccine targets for tumor immunotherapy. CT antigens, such as MAGE and NY-ESO-1, have been employed in clinical trials in various malignancies but little is known about their presence in medulloblastoma. We analyzed 25 medulloblastomas for the expression of a panel of CT antigens by RT-PCR and immunohistochemistry. Messenger RNA expression in the samples was as follows: GAGE 64%, MAGEA3/6 56%, SYCP1 44%, SLCO6A1 32%, MAGEC1 28%, MAGEC2 28%, MAGEA4 28%, NY-ESO-1 20%, MAGEA1 16%, and TPTE 0%. All cases except one (96%) were positive for mRNA expression of at least one CT gene. However, CT antigen expression was scarce on a protein level. Immunoreaction to monoclonal antibody E978 (NY-ESO-1) was negative in all cases; MA454 (MAGEA1), 57B (MAGEA4), M3H67 (MAGEA3/6), CT10#5 (MAGEC2) and #23 (GAGE) were each positive in 1 case, while the highest incidence of positive immunostaining, albeit heterogeneous, was seen with CT7-33 (MAGEC1) in 3 out of the 25 cases. The absence of correlation between mRNA and protein expression in medulloblastoma has not been observed in other tumors and further studies addressing the biology of CT antigens are necessary to investigate the present discrepant results.
Oba-Shinjo
Sueli M
SM
Department of Neurology, School of Medicine, University of São Paulo, Av Dr Arnaldo, 455, room 4110, São Paulo, Brazil.
Caballero
Otavia L
OL
Jungbluth
Achim A
AA
Rosemberg
Sergio
S
Old
Lloyd J
LJ
Simpson
Andrew J G
AJ
Marie
Suely K N
SK
D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D019496:Cancer Vaccines; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000473:pathology
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; C110905:MAGEC1 protein, human; C405429:MAGEC2 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger