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

Hum Pathol. 2017 Mar:61:130-139. doi: 10.1016/j.humpath.2016.12.006. Epub 2016 Dec 16.

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.

Keywords: Cancer-testis antigen; MAGE; NY-ESO-1; PRAME; Sarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / genetics
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Biopsy
  • Chi-Square Distribution
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Melanoma-Specific Antigens / analysis*
  • Melanoma-Specific Antigens / genetics
  • Membrane Proteins / analysis*
  • Membrane Proteins / genetics
  • Multivariate Analysis
  • Necrosis
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Sarcoma, Synovial / genetics
  • Sarcoma, Synovial / immunology*
  • Sarcoma, Synovial / pathology
  • Sarcoma, Synovial / therapy
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / immunology*
  • Soft Tissue Neoplasms / pathology
  • Soft Tissue Neoplasms / therapy
  • Time Factors
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CTAG1B protein, human
  • MAGEA1 protein, human
  • MAGEA4 protein, human
  • Melanoma-Specific Antigens
  • Membrane Proteins
  • Neoplasm Proteins
  • PRAME protein, human