title: NY-ESO-1/LAGE-1 coexpression with MAGE-A cancer/testis antigens: a tissue microarray study.
abstract: The characterization of the expression pattern of different families of cancer/testis (C/T) antigens in different tumors, at the protein level, might be of relevance in the development of multiantigen vaccine preparations for active specific immunotherapy. We have used tissue microarray (TMA) technology to explore in large numbers of tumor specimens the expression of NY-ESO-1/LAGE-1 C/T antigens and its correlation with MAGE-A expression by using D8.38 and 57B monoclonal antibodies (MAb). The epitopes recognized by these reagents in C/T antigens were identified by molecular mapping by using a bacterial expression system. Out of 2,052 samples, 119 (5.8%) scored positive upon staining with D8.38 NY-ESO-1/LAGE-1-specific MAb. Expression in >10% of cases was detectable in melanoma and basalioma (31.6 and 18.2%, respectively), large cell carcinomas and adenocarcinomas of the lung (17.8 and 10.5%, respectively), stomach adenocarcinomas of the intestinal type (13.2%), pT2-4 bladder TCC (18.2%), nonseminomatous carcinomas of the testis (10.4%) and liposarcomas (15.4%). Simultaneous expression of NY-ESO-1/LAGE-1 and MAGE-A C/T antigens was then addressed in a TMA where 101/845 and 73/845 samples (12 and 8.6%, respectively) showed evidence of MAGE-A or NY-ESO-1/LAGE-1 specific staining, respectively. In 35/845 specimens (4.1%) concomitant expression of MAGE-A and NY-ESO-1/LAGE-1 was observed (p = 0.0002). Discrepancies in the expression of NY-ESO-1/LAGE-1 and MAGE-A were conspicuously detectable in squamous cell carcinomas of the skin (MAGE-A positive but NY-ESO-1/LAGE-1 negative) and in liposarcomas (NY-ESO-1/LAGE-1 positive, but MAGE-A negative). Taken together, these data suggest novel areas of application of C/T antigens targeted active specific immunotherapy possibly based on multiantigen vaccine preparations.
authors.affiliation: Institut Chirurgische Forschung und Spitalmanagement, Department Forschung, University of Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Bolli
authors.forename: Elke
authors.initials: E
authors.lastname: Schultz-Thater
authors.forename: Paul
authors.initials: P
authors.lastname: Zajac
authors.forename: Ulrich
authors.initials: U
authors.lastname: Guller
authors.forename: Chantal
authors.initials: C
authors.lastname: Feder
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanguedolce
authors.forename: Vincenza
authors.initials: V
authors.lastname: Carafa
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Tvrtko
authors.initials: T
authors.lastname: Hudolin
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism*; D018604:Epitope Mapping; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology*; D013737:Testis / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins