Reproducing the molecular subclassification of peripheral T-cell lymphoma-NOS by immunohistochemistry

  • Blood. 2019 Dec 12;134(24):2159-2170. doi: 10.1182/blood.2019000779.
Catalina Amador  1 ,  Timothy C Greiner  1 ,  Tayla B Heavican  1 ,  Lynette M Smith  2 ,  Karen Tatiana Galvis  1  3 ,  Waseem Lone  1 ,  Alyssa Bouska  1 ,  Francesco D'Amore  4 ,  Martin Bjerregaard Pedersen  4 ,  Stefano Pileri  5  6 ,  Claudio Agostinelli  6 ,  Andrew L Feldman  7 ,  Andreas Rosenwald  8  9 ,  German Ott  10  11 ,  Anja Mottok  12  13 ,  Kerry J Savage  12 ,  Laurence de Leval  14 ,  Philippe Gaulard  15 ,  Soon Thye Lim  16 ,  Choon Kiat Ong  16 ,  Sarah L Ondrejka  17 ,  Joo Song  18 ,  Elias Campo  19  20 ,  Elaine S Jaffe  21 ,  Louis M Staudt  22 ,  Lisa M Rimsza  23 ,  Julie Vose  24 ,  Dennis D Weisenburger  18 ,  Wing C Chan  18 ,  Javeed Iqbal  1
Affiliations
  • 1. Department of Pathology and Microbiology and.
  • 2. Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE.
  • 3. Department of Pathology and Laboratory Medicine, Fundacion Santa Fe de Bogota University Hospital, Bogota, Colombia.
  • 4. Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
  • 5. European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • 6. Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy.
  • 7. Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
  • 8. Institute of Pathology and.
  • 9. Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
  • 10. Department of Clinical Pathology and.
  • 11. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
  • 12. Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada.
  • 13. Institute of Human Genetics, Ulm University/University Medical Centre, Ulm, Germany.
  • 14. Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.
  • 15. Département de Pathologie, Hôpital Henri-Mondor, Université Paris-Est, INSERM U955, Créteil, France.
  • 16. Division of Medical Oncology, National Cancer Centre Singapore/Duke-National University of Singapore (NUS) Medical School, Singapore.
  • 17. Department of Pathology, Cleveland Clinic, Cleveland, OH.
  • 18. Department of Pathology, City of Hope National Medical Center, Duarte, CA.
  • 19. Hematopathology Unit, Hospital Clinic, Barcelona, Spain.
  • 20. Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
  • 21. Laboratory of Pathology and.
  • 22. Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • 23. Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ; and.
  • 24. Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE.
PMID: 31562134 DOI: 10.1182/blood.2019000779
Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature T-cell malignancies; approximately one-third of cases are designated as PTCL-not otherwise specified (PTCL-NOS). Using gene-expression profiling (GEP), we have previously defined 2 major molecular subtypes of PTCL-NOS, PTCL-GATA3 and PTCL-TBX21, which have distinct biological differences in oncogenic pathways and prognosis. In the current study, we generated an immunohistochemistry (IHC) algorithm to identify the 2 subtypes in paraffin tissue using antibodies to key transcriptional factors (GATA3 and TBX21) and their target proteins (CCR4 and CXCR3). In a training cohort of 49 cases of PTCL-NOS with corresponding GEP data, the 2 subtypes identified by the IHC algorithm matched the GEP results with high sensitivity (85%) and showed a significant difference in overall survival (OS) (P = .03). The IHC algorithm classification showed high interobserver reproducibility among pathologists and was validated in a second PTCL-NOS cohort (n = 124), where a significant difference in OS between the PTCL-GATA3 and PTCL-TBX21 subtypes was confirmed (P = .003). In multivariate analysis, a high International Prognostic Index score (3-5) and the PTCL-GATA3 subtype identified by IHC were independent adverse predictors of OS (P = .0015). Additionally, the 2 IHC-defined subtypes were significantly associated with distinct morphological features (P < .001), and there was a significant enrichment of an activated CD8+ cytotoxic phenotype in the PTCL-TBX21 subtype (P = .03). The IHC algorithm will aid in identifying the 2 subtypes in clinical practice, which will aid the future clinical management of patients and facilitate risk stratification in clinical trials.