Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4 and MAGEA1

Publication date: Available online 16 December 2016
Source:Human Pathology
Author(s): Kunio Iura, Akira Maekawa, Kenichi Kohashi, Takeaki Ishii, Hirofumi Bekki, Hiroshi Otsuka, Yuichi Yamada, Hidetaka Yamamoto, Katsumi Harimaya, Yukihide Iwamoto, Yoshinao Oda
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 synovial sarcomas with those of three 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 (PCR) in 108 synovial sarcomas. Immunohistochemically, NY-ESO-1, PRAME, MAGEA4 and MAGEA1 were positive in 66/108 (61%), 93/108 (86%), 89/108 (82%) and 16/108 (15%) SSs, respectively, and 104/108 (96%) of the SSs showed the immunohistochemical expression of ≥1 of NY-ESO-1, PRAME and MAGEA4. Moreover, the high expression of ≥1 of these three 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 PCR results were closely related to the immunohistochemical results: NY-ESO-1 (P = .0019), PRAME (P = .039), MAGEA4 (P = .0149), 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.



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