机构：[1]Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE.[2]Biometric Research Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.[3]Department of Pathology, City of Hope National Medical Center, Duarte, CA.[4]Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN.[5]Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE.[6]European Institute of Oncology, Milan/Bologna University School of Medicine, Bologna, Italy.[7]Department of Clinical Pathology, Robert-Bosch Krankenhaus and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.[8]Institute of Pathology, University of Wurzburg, and Comprehensive Cancer Center Mainfranken, Wuerzburg, Germany.[9]Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada.[10]Sungkyunkwan University School of Medicine, Seoul, Korea.[11]Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.医技科室病理科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[12]Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH.[13]Departamento de Patologia Instituto Nacional de Enfermedades Neoplásicas, Facultad de Medicina Universidad Nacional Mayor de San Marcos, Lima, Peru.[14]Division of Medical Oncology, National Cancer Centre Singapore/Duke-NUS Medical School, Singapore, Singapore.[15]Department of Pathology, University of Miami, Miami, FL.[16]Department of Pathology and Laboratory Medicine, Weil Cornell Medical College, New York, NY.[17]Department of Pathology and Laboratory Medicine, Oregon Health &[18]Science University, Portland, OR.[18]Department of Pathology, University of Iowa, Iowa, IA.[19]Peter MacCallum Cancer Centre, Melbourne, Australia.[20]Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD.[21]Healthchart, LLC, Memphis TN.[22]Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Scottsdale, AZ.[23]Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE.[24]Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression-based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis.We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays.In the training cohort, the refined transcriptomic classifier in FFPE tissues showed high sensitivity (> 80%), specificity (> 95%), and accuracy (> 94%) for PTCL subclassification compared with the fresh-frozen-derived diagnostic model and showed high reproducibility between three independent laboratories. In the validation cohort, the transcriptional classifier matched the pathology diagnosis rendered by three expert hematopathologists in 85% (n = 119) of the cases, showed borderline association with the molecular signatures in 6% (n = 8), and disagreed in 8% (n = 11). The classifier improved the pathology diagnosis in two cases, validated by clinical findings. Of the 11 cases with disagreements, four had a molecular classification that may provide an improvement over pathology diagnosis on the basis of overall transcriptomic and morphological features. The molecular subclassification provided a comprehensive molecular characterization of PTCL subtypes, including viral etiologic factors and translocation partners.We developed a novel transcriptomic approach for PTCL subclassification that facilitates translation into clinical practice with higher precision and uniformity than conventional pathology diagnosis.
第一作者机构：[1]Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE.
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通讯作者：
推荐引用方式(GB/T 7714)：
Amador Catalina,Bouska Alyssa,Wright George,et al.Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice[J].JOURNAL OF CLINICAL ONCOLOGY.2022,40(36):4261-+.doi:10.1200/JCO.21.02707.
APA：
Amador Catalina,Bouska Alyssa,Wright George,Weisenburger Dennis D,Feldman Andrew L...&Iqbal Javeed.(2022).Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice.JOURNAL OF CLINICAL ONCOLOGY,40,(36)
MLA：
Amador Catalina,et al."Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice".JOURNAL OF CLINICAL ONCOLOGY 40..36(2022):4261-+
医学