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

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

  • Amador C Department of Pathology and Microbiology and.
  • Greiner TC Department of Pathology and Microbiology and.
  • Heavican TB Department of Pathology and Microbiology and.
  • Smith LM Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE.
  • Galvis KT Department of Pathology and Microbiology and.
  • Lone W Department of Pathology and Microbiology and.
  • Bouska A Department of Pathology and Microbiology and.
  • D'Amore F Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
  • Pedersen MB Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
  • Pileri S European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Agostinelli C Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy.
  • Feldman AL Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
  • Rosenwald A Institute of Pathology and.
  • Ott G Department of Clinical Pathology and.
  • Mottok A Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada.
  • Savage KJ Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada.
  • de Leval L Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.
  • Gaulard P Département de Pathologie, Hôpital Henri-Mondor, Université Paris-Est, INSERM U955, Créteil, France.
  • Lim ST Division of Medical Oncology, National Cancer Centre Singapore/Duke-National University of Singapore (NUS) Medical School, Singapore.
  • Ong CK Division of Medical Oncology, National Cancer Centre Singapore/Duke-National University of Singapore (NUS) Medical School, Singapore.
  • Ondrejka SL Department of Pathology, Cleveland Clinic, Cleveland, OH.
  • Song J Department of Pathology, City of Hope National Medical Center, Duarte, CA.
  • Campo E Hematopathology Unit, Hospital Clinic, Barcelona, Spain.
  • Jaffe ES Laboratory of Pathology and.
  • Staudt LM Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Rimsza LM Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ; and.
  • Vose J Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE.
  • Weisenburger DD Department of Pathology, City of Hope National Medical Center, Duarte, CA.
  • Chan WC Department of Pathology, City of Hope National Medical Center, Duarte, CA.
  • Iqbal J Department of Pathology and Microbiology and.
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  • 2019-09-29
Published in:
  • Blood. - 2019
Adult
Aged
Algorithms
Biomarkers, Tumor
Computational Biology
Female
Gene Expression Profiling
Humans
Immunohistochemistry
Immunophenotyping
Lymphoma, T-Cell, Peripheral
Male
Middle Aged
Neoplasm Staging
Prognosis
Reproducibility of Results
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/29660
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