2. Academic Validation
  3. Reproducing the molecular subclassification of peripheral T-cell lymphoma-NOS by immunohistochemistry

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

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.

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