title: Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T-cell epitope in a patient with bladder cancer.
abstract: Cancer-testis (CT) antigens are ideal vaccine targets since their expression is restricted in adult tissues to testicular germ cells and a subset of cancers. The frequency of expression in transitional cell carcinomas (TCCs) of NY-ESO-1, the most immunogenic CT antigen to date, and its closely related gene LAGE-1 was studied. NY-ESO-1 and LAGE-1 antigen expression were found to occur frequently in high-grade TCC tumors. On an MSKCC IRB-approved protocol, 68 patient specimens were collected prospectively at the time of transurethral resection or cystectomy, of which 43 were read pathologically as high-grade tumors (pCIS, pTaG3, pT1, pT2, pT3, and pT4), 8 as low-grade tumors (pTaG1, pTaG2), and 17 as disease-free samples. These 68 samples were analyzed by immunohistochemistry (IHC) and/or RT-PCR. There were also an additional 53 paraffin-embedded specimens studied retrospectively by IHC, of which 39 were high-grade tumors and 14 were low-grade tumors. Cumulatively, our data indicate that NY-ESO-1 and/or LAGE-1 are expressed in 39/82 (48%) high-grade TCC and 3/22 (14%) low-grade TCC samples when analyzed by RT-PCR and/or IHC. Immunological assessment of these patients' sera identified one patient, whose tumor homogeneously expressed NY-ESO-1, which had detectable antibodies against NY-ESO-1 and LAGE-1. Further analysis of this patient, who remains clinically without evidence of disease 24 months after cystectomy for high-grade pT4 disease, revealed T-cell immunity against NY-ESO-1. This patient's T-cell response was determined to be specific for a new NY-ESO-1 epitope, p94-102, in the context of HLA-B35.
authors.affiliation: Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. sharmap@mskcc.org
authors.forename: Padmanee
authors.initials: P
authors.lastname: Sharma
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Barbara
authors.initials: B
authors.lastname: Williamson
authors.forename: Harry
authors.initials: H
authors.lastname: Herr
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stockert
authors.forename: Guido
authors.initials: G
authors.lastname: Dalbagni
authors.forename: S Machele
authors.initials: SM
authors.lastname: Donat
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Darren
authors.initials: D
authors.lastname: Santiago
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000276:immunology; D000954:Antigens, Surface; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger