title: Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1.
abstract: Synovial sarcoma (SS) is regarded as a relatively chemosensitive sarcoma, but the prognosis of advanced SSs remains poor. Here we identified highly expressed cancer-testis antigens that could be promising immunotherapy targets for SS, using a previously conducted cDNA microarray, and we assessed the clinicopathological or prognostic relationships of these antigens in SS. We compared the gene expression profiles of 11 SSs with those of 3 normal adipose tissues. Among the up-regulated cancer-testis antigens, we analyzed PRAME, MAGEA1, and MAGEA4 and another cancer-testis antigen (NY-ESO-1) together, by immunohistochemistry and real-time polymerase chain reaction in 108 SSs. Immunohistochemically, NY-ESO-1, PRAME, MAGEA4, and MAGEA1 were positive in 66 (61%), 93 (86%), 89 (82%), and 16 (15%) of 108 SSs, respectively, and 104 (96%) of 108 SSs showed the immunohistochemical expression of at least 1 of NY-ESO-1, PRAME, and MAGEA4. Moreover, the high expression of at least 1 of these 3 antigens was observed in 83% of the SSs. High expression of NY-ESO-1 and MAGEA4 was significantly correlated with the presence of necrosis and advanced clinical stage. The immunohistochemical expression of these cancer-testis antigens was not correlated with prognosis, but the coexpression of NY-ESO-1, PRAME, and MAGEA4 was significantly associated with adverse prognosis. The real-time polymerase chain reaction results were closely related to the immunohistochemical results: NY-ESO-1 (P = .0019), PRAME (P = .039), MAGEA4 (P = .0149), and MAGEA1 (P = .0766). These data support the potential utility of NY-ESO-1, PRAME, and MAGEA4 as immunotherapy targets and ancillary prognostic parameters, suggesting the possible benefit of the combined use of these cancer-testis antigens as an SS immunotherapy target.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Iura
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Maekawa
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kohashi
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Bekki
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Otsuka
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Harimaya
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: oda@surgpath.med.kyushu-u.ac.jp.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D058950:Melanoma-Specific Antigens / Q000032:analysis* / Q000235:genetics; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D015999:Multivariate Analysis; D009336:Necrosis; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013584:Sarcoma, Synovial / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C104948:CTAG1B protein, human; C072011:MAGEA1 protein, human; C095204:MAGEA4 protein, human; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C404944:PRAME protein, human
keywords: Cancer-testis antigen; MAGE; NY-ESO-1; PRAME; Sarcoma