Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patient Cohort
2.2. Cancer-Testis Antigens Show Distinct Expression Patterns in Sarcoma Subtypes
2.3. Cancer-Testis Antigens PRAME and NY-ESO-1 Are Expressed More Frequently in Soft Tissue Sarcomas with Low Counts of Tumour-Infiltrating Lymphocytes
2.4. Expression of PRAME and NY-ESO-1 Is Associated with Grading in Opposing Ways
2.5. PRAME Expression Is Prognostic of Shorter Survival while NY-ESO-1 Is Associated with a More Favourable Prognosis
2.6. Expression of CTAs PRAME und SSX2 As Well As Radical Resections, Chemotherapy, and Metastatic Disease Influenced Overall Surivival in Multivariate Analysis
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Histopathology and Tissue Microarray Construction Immunohistochemistry
4.3. Immunohistochemistry of Cancer Testis Antigens
4.4. Tumour-Infiltrating Lymphocytes
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Expression | PRAME | NY-ESO-1 | SSX2 | |||
---|---|---|---|---|---|---|
n | % | n | % | n | % | |
0 | 224 | 90.0 | 214 | 85.9 | 237 | 95.6 |
1 | 6 | 2.4 | 8 | 3.2 | 2 | 0.8 |
2 | 8 | 3.2 | 8 | 3.2 | 4 | 1.6 |
3 | 11 | 4.4 | 19 | 7.6 | 5 | 2.0 |
Total | 249 | 100.0 | 249 | 100.0 | 248 | 100.0 |
Missing | 1 |
HR (95% CI) | p | ||
---|---|---|---|
Metastatic disease | M0 | 1 | <0.001 |
M1 | 3.173 (1.889–5.330) | ||
Surgical margins | R0/R1 | 1 | <0.001 |
R2 or no resection | 1.618 (1.328–1.972) | ||
PRAME | Low | 1 | 0.117 |
High | 1.181 (0.959–1.453) | ||
SSX2 | High | 1 | 0.229 |
Low | 1.841 (0.681–4.982) | ||
NY-ESO-1 | High | 1 | 0.096 |
Low | 1.600 (0.921–2.782) | ||
TILs count | Low | 1 | 0.635 |
High | 1.207 (0.804–1.811) | ||
Histological subgroup | 1.061 (1.007–1.119) | 0.028 | |
Radiotherapy | Not done | 1 | 0.455 |
Done | 1.166 (0.779–1.743) | ||
Regional hyperthermia | Not done | 1 | 0.085 |
Done | 1.446 (0.950–2.200) |
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n | % | ||
---|---|---|---|
Total | 249 | 100 | |
Sex | Male | 124 | 50 |
Female | 125 | 50 | |
Histological subtype | UPS | 82 | 33 |
Leiomyosarcoma | 50 | 20 | |
Synovial sarcoma | 28 | 11 | |
Dedifferentiated Liposarcoma | 47 | 19 | |
Angiosarcoma | 9 | 4 | |
MPNST | 13 | 5 | |
Other | 20 | 8 | |
Location | Extremities | 85 | 34 |
Retroperitoneal | 54 | 22 | |
Abdominal/visceral | 42 | 17 | |
Trunk | 60 | 24 | |
Other | 8 | 3 | |
Grading | Intermediate (G2) | 118 | 47 |
High (G3) | 131 | 53 | |
Size | <50 mm | 20 | 8 |
50–79 mm | 61 | 24 | |
80–120 mm | 64 | 26 | |
>120 mm | 76 | 31 | |
Missing | 28 | 11 | |
Metastatic disease | M0 | 227 | 91 |
M1 | 22 | 9 | |
Surgical margins | R0/R1 | 202 | 81 |
R2 or no resection | 47 | 19 | |
Radiotherapy | Done | 53 | 21 |
Not done | 180 | 72 | |
Unknown | 16 | 2 | |
Regional hyperthermia | Done | 195 | 78 |
Not done | 54 | 22 |
Total | PRAME | NY-ESO-1 | SSX2 | TILs | |||||
---|---|---|---|---|---|---|---|---|---|
Histologic Subtype | n | n | % | n | % | n | % | n | % |
UPS | 82 a | 6 | 7% | 2 | 2% | 3 | 4% | 71 | 87% |
Leiomyosarcoma | 50 | 3 | 6% | 1 | 2% | 0 | 0% | 33 | 66% |
Synovial Sarcoma | 28 | 3 | 11% | 12 | 43% | 7 | 25% | 13 | 46% |
DDLPS | 47 | 2 | 4% | 3 | 6% | 0 | 0% | 39 | 83% |
Angiosarcoma | 9 | 3 | 33% | 1 | 11% | 0 | 0% | 8 | 89% |
MPNST | 13 | 5 | 38% | 0 | 0% | 1 | 8% | 11 | 85% |
Other | 20 | 3 | 15% | 0 | 0% | 0 | 0% | 18 | 90% |
Total | 249 a | 25 | 10% | 19 | 8% | 11 | 4% | 193 | 78% |
HR (95% CI) | p | ||
---|---|---|---|
Metastatic disease | M0 | 1 | <0.001 |
M1 | 3.182 (1.875–5.401) | ||
Surgical margins | R0/R1 | 1 | <0.001 |
R2 or no resection | 2.531 (1.682–3.809) | ||
PRAME | Low | 1 | <0.001 |
High | 2.675 (1.548–4.622) | ||
SSX2 | High | 1 | 0.039 |
Antigen | Product No. | Supplier | Clone | Dilution | Pre-Treatment |
---|---|---|---|---|---|
NY-ESO-1 | SC-53869 | Santa Cruz | E978 | 1:100 | ER2 |
PRAME | ab219650 | Abcam | EPR20330 | 1:1000 | ER2 |
SSX2 | AMAb91141 | Atlas Antibodies | CL3202 | 1:3000 | ER2 |
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Albertsmeier, M.; Altendorf-Hofmann, A.; Lindner, L.H.; Issels, R.D.; Kampmann, E.; Dürr, H.-R.; Schubert-Fritschle, G.; Angele, M.K.; Kirchner, T.; Jungbluth, A.A.; et al. Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma. Cancers 2020, 12, 3612. https://doi.org/10.3390/cancers12123612
Albertsmeier M, Altendorf-Hofmann A, Lindner LH, Issels RD, Kampmann E, Dürr H-R, Schubert-Fritschle G, Angele MK, Kirchner T, Jungbluth AA, et al. Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma. Cancers. 2020; 12(12):3612. https://doi.org/10.3390/cancers12123612
Chicago/Turabian StyleAlbertsmeier, Markus, Annelore Altendorf-Hofmann, Lars H. Lindner, Rolf D. Issels, Eric Kampmann, Hans-Roland Dürr, Gabriele Schubert-Fritschle, Martin K. Angele, Thomas Kirchner, Achim A. Jungbluth, and et al. 2020. "Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma" Cancers 12, no. 12: 3612. https://doi.org/10.3390/cancers12123612
APA StyleAlbertsmeier, M., Altendorf-Hofmann, A., Lindner, L. H., Issels, R. D., Kampmann, E., Dürr, H.-R., Schubert-Fritschle, G., Angele, M. K., Kirchner, T., Jungbluth, A. A., & Knösel, T. (2020). Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma. Cancers, 12(12), 3612. https://doi.org/10.3390/cancers12123612