Trophoblast Cell Surface Antigen 2 (Trop2) Is Expressed in Cases of EBV-Positive Diffuse Large B-Cell Lymphoma Emerging from Angioimmunoblastic T-Cell Lymphoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Tissue Microarray (TMA)
2.3. Immunohistochemistry (IHC)
2.4. Endpoints
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Immunohistochemical Findings
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Armitage, J.O.; Gascoyne, R.D.; Lunning, M.A.; Cavalli, F. Non-Hodgkin lymphoma. Lancet 2017, 390, 298–310. [Google Scholar] [CrossRef] [PubMed]
- Ghandili, S.; Dierlamm, J.; Bokemeyer, C.; von Bargen, C.M.; Weidemann, S.A. NTRK fusion protein expression is absent in a large cohort of diffuse large B-cell lymphoma. Front. Oncol. 2023, 13, 1146029. [Google Scholar] [CrossRef] [PubMed]
- Melchardt, T.; Egle, A.; Greil, R. How I treat diffuse large B-cell lymphoma. ESMO Open 2023, 8, 100750. [Google Scholar] [CrossRef]
- Hui, D.; Proctor, B.; Donaldson, J.; Shenkier, T.; Hoskins, P.; Klasa, R.; Savage, K.; Chhanabhai, M.; Gascoyne, R.D.; Connors, J.M.; et al. Prognostic implications of extranodal involvement in patients with diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone. Leuk. Lymphoma 2010, 51, 1658–1667. [Google Scholar] [CrossRef] [PubMed]
- Rossi, D.; Spina, V.; Gaidano, G. Biology and treatment of Richter syndrome. Blood 2018, 131, 2761–2772. [Google Scholar] [CrossRef]
- Wagner-Johnston, N.D.; Link, B.K.; Byrtek, M.; Dawson, K.L.; Hainsworth, J.; Flowers, C.R.; Friedberg, J.W.; Bartlett, N.L. Outcomes of transformed follicular lymphoma in the modern era: A report from the National LymphoCare Study (NLCS). Blood 2015, 126, 851–857. [Google Scholar] [CrossRef] [PubMed]
- Biasoli, I.; Stamatoullas, A.; Meignin, V.; Delmer, A.; Reman, O.; Morschhauser, F.; Coiffier, B.; Bosly, A.; Divine, M.; Brice, P. Nodular, lymphocyte-predominant Hodgkin lymphoma: A long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group. Cancer 2010, 116, 631–639. [Google Scholar] [CrossRef] [PubMed]
- Hartmann, S.; Eray, M.; Doring, C.; Lehtinen, T.; Brunnberg, U.; Kujala, P.; Vornanen, M.; Hansmann, M.-L. Diffuse large B cell lymphoma derived from nodular lymphocyte predominant Hodgkin lymphoma presents with variable histopathology. BMC Cancer 2014, 14, 332. [Google Scholar] [CrossRef] [PubMed]
- Xu, Y.; McKenna, R.W.; Hoang, M.P.; Collins, R.H.; Kroft, S.H. Composite angioimmunoblastic T-cell lymphoma and diffuse large B-cell lymphoma: A case report and review of the literature. Am. J. Clin. Pathol. 2002, 118, 848–854. [Google Scholar] [CrossRef]
- Yang, Q.X.; Pei, X.J.; Tian, X.Y.; Li, Y.; Li, Z. Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: A case report and review of literature. Diagn. Pathol. 2012, 7, 7. [Google Scholar] [CrossRef]
- Dunleavy, K.; Wilson, W.H.; Jaffe, E.S. Angioimmunoblastic T cell lymphoma: Pathobiological insights and clinical implications. Curr. Opin. Hematol. 2007, 14, 348–353. [Google Scholar] [CrossRef] [PubMed]
- Attygalle, A.D.; Kyriakou, C.; Dupuis, J.; Grogg, K.L.; Diss, T.C.; Wotherspoon, A.C.; Chuang, S.S.; Cabeçadas, J.; Isaacson, P.G.F.; Du, M.-Q.M.; et al. Histologic evolution of angioimmunoblastic T-cell lymphoma in consecutive biopsies: Clinical correlation and insights into natural history and disease progression. Am. J. Surg. Pathol. 2007, 31, 1077–1088. [Google Scholar] [CrossRef] [PubMed]
- Pavlovsky, M.; Cubero, D.; Agreda-Vasquez, G.P.; Enrico, A.; Mela-Osorio, M.J.; San Sebastian, J.A.; Fogliatto, L.; Ovilla, R.; Avendano, O.; Machnicki, G.; et al. Clinical Outcomes of Patients With B-Cell Non-Hodgkin Lymphoma in Real-World Settings: Findings from the Hemato-Oncology Latin America Observational Registry Study. JCO Glob. Oncol. 2022, 8, e2100265. [Google Scholar] [CrossRef] [PubMed]
- Bishop, M.R.; Dickinson, M.; Purtill, D.; Barba, P.; Santoro, A.; Hamad, N.; Kato, K.; Sureda, A.; Greil, R.; Thieblemont, C.; et al. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N. Engl. J. Med. 2022, 386, 629–639. [Google Scholar] [CrossRef] [PubMed]
- Hutchings, M.; Mous, R.; Clausen, M.R.; Johnson, P.; Linton, K.M.; Chamuleau, M.E.D.; Lewis, D.J.; Balari, A.S.; Cunningham, D.; Oliveri, R.S.; et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: An open-label, phase 1/2 study. Lancet 2021, 398, 1157–1169. [Google Scholar] [CrossRef] [PubMed]
- Dickinson, M.J.; Carlo-Stella, C.; Morschhauser, F.; Bachy, E.; Corradini, P.; Iacoboni, G.; Khan, C.; Wróbel, T.; Offner, F.; Trněný, M.; et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N. Engl. J. Med. 2022, 387, 2220–2231. [Google Scholar] [CrossRef]
- Hutchings, M.; Morschhauser, F.; Iacoboni, G.; Carlo-Stella, C.; Offner, F.C.; Sureda, A.; Salles, G.; Martínez-Lopez, J.; Crump, M.; Thomas, D.N.; et al. Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. J. Clin. Oncol. 2021, 39, 1959–1970. [Google Scholar] [CrossRef] [PubMed]
- Locke, F.L.; Miklos, D.B.; Jacobson, C.A.; Perales, M.A.; Kersten, M.J.; Oluwole, O.O.; Ghobadi, A.; Rapoport, A.P.; McGuirk, J.; Pagel, J.M.; et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N. Engl. J. Med. 2022, 386, 640–654. [Google Scholar] [CrossRef] [PubMed]
- Kamdar, M.; Solomon, S.R.; Arnason, J.; Johnston, P.B.; Glass, B.; Bachanova, V.; Ibrahimi, S.; Mielke, S.; Mutsaers, P.; Hernandez-Ilizaliturri, F.; et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet 2022, 399, 2294–2308. [Google Scholar]
- Zaman, S.; Jadid, H.; Denson, A.C.; Gray, J.E. Targeting Trop-2 in solid tumors: Future prospects. Onco Targets Ther. 2019, 12, 1781–1790. [Google Scholar] [CrossRef]
- Vranic, S.; Gatalica, Z. Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers. Bosn. J. Basic. Med. Sci. 2022, 22, 14–21. [Google Scholar] [CrossRef]
- Lipinski, M.; Parks, D.R.; Rouse, R.V.; Herzenberg, L.A. Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc. Natl. Acad. Sci. USA 1981, 78, 5147–5150. [Google Scholar] [CrossRef] [PubMed]
- Stepan, L.P.; Trueblood, E.S.; Hale, K.; Babcook, J.; Borges, L.; Sutherland, C.L. Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: Potential implications as a cancer therapeutic target. J. Histochem. Cytochem. 2011, 59, 701–710. [Google Scholar] [CrossRef]
- Goldenberg, D.M.; Stein, R.; Sharkey, R.M. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget 2018, 9, 28989–29006. [Google Scholar] [CrossRef] [PubMed]
- FDAUS. FDA Approves Sacituzumab Govitecan-Hziy for HR-Positive Breast Cancer 2023. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-hr-positive-breast-cancer (accessed on 23 June 2023).
- FDA US. FDA Grants Regular Approval to Sacituzumab Govitecan for Triple-Negative Breast Cancer 2021. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer (accessed on 23 June 2023).
- FDA US. FDA Grants Accelerated Approval to Sacituzumab Govitecan for Advanced Urothelial Cancer 2021. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer (accessed on 23 June 2023).
- Dum, D.; Taherpour, N.; Menz, A.; Hoflmayer, D.; Volkel, C.; Hinsch, A.; Gorbokon, N.; Lennartz, M.; Hube-Magg, C.; Fraune, C.; et al. Trophoblast Cell Surface Antigen 2 Expression in Human Tumors: A Tissue Microarray Study on 18,563 Tumors. Pathobiology 2022, 89, 245–258. [Google Scholar] [CrossRef] [PubMed]
- Bobos, M.; Kotoula, V.; Kaloutsi, V.; Karayannopoulou, G.; Papadimitriou, C.S.; Kostopoulos, I. Aberrant CCND1 copies and cyclin D1 mRNA expression do not result in the production of functional cyclin D1 protein in anaplastic large cell lymphoma. Histol. Histopathol. 2009, 24, 1035–1048. [Google Scholar]
- Chen, R.; Lu, M.; Wang, J.; Zhang, D.; Lin, H.; Zhu, H.; Zhang, W.; Xiong, L.; Ma, J.; Mao, Y.; et al. Increased expression of Trop2 correlates with poor survival in extranodal NK/T cell lymphoma, nasal type. Virchows Arch. 2013, 463, 713–719. [Google Scholar] [CrossRef]
- Lister, T.A.; Crowther, D.; Sutcliffe, S.B.; Glatstein, E.; Canellos, G.P.; Young, R.C.; Rosenberg, S.A.; Coltman, C.A.; Tubiana, M. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J. Clin. Oncol. 1989, 7, 1630–1636. [Google Scholar] [CrossRef] [PubMed]
- International Non-Hodgkin’s Lymphoma Prognostic Factors P. A predictive model for aggressive non-Hodgkin’s lymphoma. N. Engl. J. Med. 1993, 329, 987–994. [Google Scholar] [CrossRef]
- Kononen, J.; Bubendorf, L.; Kallioniemi, A.; Barlund, M.; Schraml, P.; Leighton, S.; Torhorst, J.; Mihatsch, M.J.; Sauter, G.; Kallionimeni, O.-P. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat. Med. 1998, 4, 844–847. [Google Scholar] [CrossRef]
- Zettl, A.; Lee, S.S.; Rudiger, T.; Starostik, P.; Marino, M.; Kirchner, T.; Ott, M.; Muller-Hermelink, H.K.; Ott, G. Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angloimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Am. J. Clin. Pathol. 2002, 117, 368–379. [Google Scholar] [CrossRef]
- Petit, B.; Le Meur, Y.; Jaccard, A.; Paraf, F.; Robert, C.L.; Bordessoule, D.; Labrousse, F.; Drouet, M. Influence of host-recipient origin on clinical aspects of posttransplantation lymphoproliferative disorders in kidney transplantation. Transplantation 2002, 73, 265–271. [Google Scholar] [CrossRef]
- Martinez, O.M.; Krams, S.M. The Immune Response to Epstein Barr Virus and Implications for Posttransplant Lymphoproliferative Disorder. Transplantation 2017, 101, 2009–2016. [Google Scholar] [CrossRef]
- Leblond, V.; Choquet, S. Lymphoproliferative disorders after liver transplantation. J. Hepatol. 2004, 40, 728–735. [Google Scholar] [CrossRef]
Total number of analyzable patients, n | 91 |
Age at DLBCL diagnosis, median (range) | 74 (32–90) |
Female sex, n (%) | 37 (40) |
Subtypes, n (%) | |
Cell of origin type: Germinal center B-cell-like | 41 (45) |
Epstein-Barr-virus positivity | 4 (4) |
Double hit | 2 (2) |
Triple hit | 0 |
Ann Arbor stage, n (%) | |
1A or 1B and 2A or 2B | 18 (20) |
3A or 3B | 5 (5) |
4A or 4B | 14 (15) |
Not evaluable | 59 (65) |
International Prognostic Index, n (%) | |
0–1 | 12 (13) |
2–3 | 13 (14) |
4–5 | 4 (4) |
Not evaluable | 62 (68) |
Age in Years | Sex | Tissue Origin | Trop2 Staining Intensity | Refer to Figure | |
---|---|---|---|---|---|
Case 1 | 56 | Female | Lymph node | 3+ | 4A |
Case 2 | 84 | Female | Lymph node | 0 | NA |
Case 3 | 48 | Female | Lymph node | 0 | NA |
Case 4 | 81 | Female | Lymph node | 3+ | 4B |
Case 5 | 48 | Female | Skin | 0 | NA |
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Ghandili, S.; Dierlamm, J.; Bokemeyer, C.; von Bargen, C.M.; Menz, A.; Weidemann, S.A. Trophoblast Cell Surface Antigen 2 (Trop2) Is Expressed in Cases of EBV-Positive Diffuse Large B-Cell Lymphoma Emerging from Angioimmunoblastic T-Cell Lymphoma. Reports 2024, 7, 37. https://doi.org/10.3390/reports7020037
Ghandili S, Dierlamm J, Bokemeyer C, von Bargen CM, Menz A, Weidemann SA. Trophoblast Cell Surface Antigen 2 (Trop2) Is Expressed in Cases of EBV-Positive Diffuse Large B-Cell Lymphoma Emerging from Angioimmunoblastic T-Cell Lymphoma. Reports. 2024; 7(2):37. https://doi.org/10.3390/reports7020037
Chicago/Turabian StyleGhandili, Susanne, Judith Dierlamm, Carsten Bokemeyer, Clara Marie von Bargen, Anne Menz, and Sören Alexander Weidemann. 2024. "Trophoblast Cell Surface Antigen 2 (Trop2) Is Expressed in Cases of EBV-Positive Diffuse Large B-Cell Lymphoma Emerging from Angioimmunoblastic T-Cell Lymphoma" Reports 7, no. 2: 37. https://doi.org/10.3390/reports7020037