Markus Albertsmeier1, Annelore Altendorf-Hofmann2, Lars H Lindner3, Rolf D Issels3, Eric Kampmann3, Hans-Roland Dürr4, Gabriele Schubert-Fritschle5, Martin K Angele1, Thomas Kirchner6, Achim A Jungbluth7, Thomas Knösel6. 1. Department of General, Visceral and Transplantation Surgery, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Marchioninistr. 15, 81377 Munich, Germany. 2. Department of General, Visceral and Vascular Surgery, Friedrich-Schiller Universität Jena, Am Klinikum 1, 07743 Jena, Germany. 3. Department of Internal Medicine III, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Marchioninistr. 15, 81377 Munich, Germany. 4. Musculoskeletal Oncology, Department of Orthopaedic Surgery, Physical Medicine and Rehabilitation, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Marchioninistr. 15, 81377 Munich, Germany. 5. Munich Cancer Registry (MCR) of the Munich Tumour Centre (TZM), Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Marchioninistr. 15, 81377 Munich, Germany. 6. Institute of Pathology, Ludwig-Maximilians-Universität (LMU) Munich, Thalkirchner Str. 36, 80337 Munich, Germany. 7. Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 1275, USA.
Abstract
(1) Background: PRAME, NY-ESO-1, and SSX2 are cancer testis antigens (CTAs), which are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: On a protein level, we examined PRAME, NY-ESO-1, and SSX2 expression in tumour tissues of 249 high-risk STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including tumour-infiltrating lymphocyte (TIL) counts, grading, and long-term survival. (3) Results: Expression of PRAME, NY-ESO-1, and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo-subtypes. Expression of PRAME was associated with shorter patient survival (p = 0.005) and higher grade (G2 vs. G3, p = 0.001), while NY-ESO-1 expression was correlated with more favourable survival (p = 0.037) and lower grade (G2 vs. G3, p = 0.029). Both PRAME and NY-ESO-1 expression were more frequent in STS with low TIL counts. In multivariate analysis, high PRAME and low SSX2 expression levels as well as metastatic disease and non-radical resections were independent predictors of shorter overall survival. (4) Conclusions: CTAs PRAME, NY-ESO-1, and SSX2 show distinct expression patterns in different STS subtypes. These results demonstrate their prognostic relevance and may guide future immunotherapeutic approaches in STS.
(1) Background: PRAME, NY-ESO-1, and SSX2 are cancer testis antigens (CTAs), which are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: On a protein level, we examined PRAME, NY-ESO-1, and SSX2 expression in tumour tissues of 249 high-risk STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including tumour-infiltrating lymphocyte (TIL) counts, grading, and long-term survival. (3) Results: Expression of PRAME, NY-ESO-1, and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo-subtypes. Expression of PRAME was associated with shorter patient survival (p = 0.005) and higher grade (G2 vs. G3, p = 0.001), while NY-ESO-1 expression was correlated with more favourable survival (p = 0.037) and lower grade (G2 vs. G3, p = 0.029). Both PRAME and NY-ESO-1 expression were more frequent in STS with low TIL counts. In multivariate analysis, high PRAME and low SSX2 expression levels as well as metastatic disease and non-radical resections were independent predictors of shorter overall survival. (4) Conclusions: CTAs PRAME, NY-ESO-1, and SSX2 show distinct expression patterns in different STS subtypes. These results demonstrate their prognostic relevance and may guide future immunotherapeutic approaches in STS.
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