NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis

Our plain-English summary of NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis, by J.P. Lai, P.F. Robbins, M. Raffeld, et al (Modern Pathology, 2012).

The study

• Authors: J.P. Lai, P.F. Robbins, M. Raffeld, P.P. Aung, M. Tsokos, S.A. Rosenberg, M.M. Miettinen, C.C. Lee
• Journal: Modern Pathology
• Published: 2012;25(6):854-8
• Cited by: 98 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A promising targeted therapy against NY-ESO-1 (CTAG 1B) using genetically modified T-cells in synovial sarcomas was recently demonstrated in a clinical trial at the NCI. To investigate the role of NY-ESO-1 immunohistochemistry in patient selection and gain better insight into the incidence of NY-ESO-1 expression in synovial sarcomas and other mesenchymal tumors, we evaluated NY-ESO-1 expression by immunohistochemistry in 417 tumors. This collection of samples included: 50 SS18/SSX1/2 fusion positive synovial sarcomas, 155 gastrointestinal stromal tumors (GIST), 135 other spindle cell sarcomas as well as 77 other sarcomas (chondrosarcoma, osteosarcoma, dedifferentiated liposarcoma, alveolar soft part sarcoma, rhabdomyosarcoma, angiosarcoma, malignant mesothelioma, and Ewing's sarcoma). We report that 76% of synovial sarcomas expressed NY-ESO-1 in a strong and diffuse pattern (2-3+, >50-70% of tumor cells). In contrast, only rare cases of other spindle cell mesenchymal tumor expressed NY-ESO-1 (GIST (2/155), malignant peripheral nerve sheath tumors (1/34), and dermatofibrosarcoma protuberans (2/20)). Individual cases of other sarcomas (angiosarcoma, malignant mesothelioma, chondrosarcoma, osteosarcoma, dedifferentiated liposarcoma, alveolar soft part sarcoma, and Ewing's sarcoma) were positive for NY-ESO-1. However, no positive cases were identified amongst our cohort of leiomyosarcomas (0/24), hemangiopericytoma/solitary fibrous tumors (0/40), and cellular schwannomas (0/17). In summary, we find that NY-ESO-1 is strongly and diffusely expressed in a majority of synovial sarcomas, but only rarely in other mesenchymal lesions. Beyond its role in patient selection for targeted therapy, immunohistochemistry for NY-ESO-1 may be diagnostically useful for the distinction of synovial sarcoma from other spindle cell neoplasms.

In plain English

This laboratory study, by authors at the US National Cancer Institute, did not examine asbestos exposure. The authors stained 417 tumor samples for NY-ESO-1, a protein targeted by an experimental T-cell therapy. The samples included 50 stage IV synovial sarcomas, 155 gastrointestinal stromal tumors (GISTs), 27 malignant mesotheliomas and other sarcomas. Strong, widespread staining appeared in 76% of synovial sarcomas (38/50), and 82% were positive overall. Other tumors were rarely positive: 1 of 34 malignant peripheral nerve sheath tumors, 2 of 20 dermatofibrosarcoma protuberans and 2 of 20 angiosarcomas, while 151 of 155 GISTs were negative. None of the 27 malignant mesotheliomas, 18 Ewing's sarcomas, 24 leiomyosarcomas or 17 cellular schwannomas was positive. Synovial sarcomas were positive significantly more often than the other spindle cell tumors (P less than 0.0001). The authors concluded that NY-ESO-1 staining has a role in selecting synovial sarcoma patients for targeted therapy and can reinforce a diagnosis of synovial sarcoma. They noted that some tumor types had too few samples to estimate how often they express the protein.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory pathology study: immunohistochemical staining of tumor tissue samples for the NY-ESO-1 protein, with comparison of positive rates between tumor types (Fisher's exact test)
• Who was studied: 417 tumor samples. These comprised 50 stage IV synovial sarcomas confirmed by SS18/SSX1/2 fusion and 155 GISTs. They also included 34 malignant peripheral nerve sheath tumors, leiomyosarcomas (20 in the methods, 24 in the results and table), 40 hemangiopericytoma/solitary fibrous tumors, 20 dermatofibrosarcoma protuberans, 17 cellular schwannomas, 20 angiosarcomas, 18 Ewing's sarcomas, 27 malignant mesotheliomas and 12 other sarcomas. The article does not state where or when the samples were collected.
• Exposure: No asbestos or other environmental exposure was studied. The factor measured was NY-ESO-1 protein in tumor tissue, detected by immunohistochemistry.
• Main results:
  • Synovial sarcomas: 76% (38/50) showed diffuse, moderate-to-strong staining. Three showed weak focal staining and nine were negative.
  • Synovial sarcomas: 82% (41/50) were positive for NY-ESO-1 overall.
  • Other spindle cell tumors were rarely positive: 1/34 malignant peripheral nerve sheath tumors and 2/20 dermatofibrosarcoma protuberans. None were positive among 24 leiomyosarcomas, 17 cellular schwannomas or 40 hemangiopericytoma/solitary fibrous tumors. Synovial sarcomas were positive significantly more often than these tumors (P less than 0.0001).
  • GISTs: 98% (151/155) were negative. One gastric and one intestinal GIST showed high-level staining, and two gastric GISTs showed minimal staining.
  • Malignant mesothelioma: 0 of 27 cases were positive. Ewing's sarcoma (0/18) and osteosarcoma (0/4) were also negative.
  • Positive cases among other sarcomas: angiosarcoma 2/20 (10%), chondrosarcoma 1/2, dedifferentiated liposarcoma 1/1 and undifferentiated sarcoma 1/1.
• The authors' conclusion: The authors concluded that NY-ESO-1 immunohistochemistry has a role in selecting synovial sarcoma patients for targeted therapy. They also concluded it can reinforce a diagnosis of synovial sarcoma and help distinguish it from other spindle cell tumors such as leiomyosarcoma, cellular schwannoma and dermatofibrosarcoma protuberans.
• Limitations the authors state:
  • Only very small numbers of chondrosarcoma, dedifferentiated liposarcoma and undifferentiated sarcoma were tested. The authors said more cases are needed to determine how often these tumors express NY-ESO-1.

Topics

Medical terms in this study, explained in our Lexicon: Synovial Sarcoma, Mesenchymal Tumor, Targeted Therapy, Differential Diagnosis, Clinical Trial, Immunohistochemistry, Spindle Cell, Sarcoma.

Related studies

• The diagnostic utility of reduced immunohistochemical expression of SMARCB1 in synovial sarcomas: a validation study — J. Ito, N. Asano, et al. (2016)
• Pleural malignant mesothelioma versus pleuropulmonary synovial sarcoma: a clinicopathological study of 22 cases with molecular analysis and survival data — S. Klebe, S. Prabhakaran, et al. (2018)
• Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma — M. Miettinen, J. Limon, et al. (2001)
• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA — D.W. Henderson, G. Reid, et al. (2013)
• Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases — A.G. Nicholson, P. Goldstraw, et al. (1998)
• Pericardial synovial sarcoma, a potential for misdiagnosis: clinicopathologic and molecular cytogenetic analysis of three cases with literature review — Y. Cheng, W. Sheng, et al. (2012)

Browse more research in Modern Pathology, or return to medical research.