TY - JOUR
T1 - Reproducing the molecular subclassification of peripheral T-cell lymphoma–NOS by immunohistochemistry
AU - on behalf of the Lymphoma/Leukemia Molecular Profiling Project
AU - Amador, Catalina
AU - Greiner, Timothy C.
AU - Heavican, Tayla B.
AU - Smith, Lynette M.
AU - Galvis, Karen Tatiana
AU - Lone, Waseem
AU - Bouska, Alyssa
AU - D’Amore, Francesco
AU - Pedersen, Martin Bjerregaard
AU - Pileri, Stefano
AU - Agostinelli, Claudio
AU - Feldman, Andrew L.
AU - Rosenwald, Andreas
AU - Ott, German
AU - Mottok, Anja
AU - Savage, Kerry J.
AU - de Leval, Laurence
AU - Gaulard, Philippe
AU - Lim, Soon Thye
AU - Ong, Choon Kiat
AU - Ondrejka, Sarah L.
AU - Song, Joo
AU - Campo, Elias
AU - Jaffe, Elaine S.
AU - Staudt, Louis M.
AU - Rimsza, Lisa M.
AU - Vose, Julie
AU - Weisenburger, Dennis D.
AU - Chan, Wing C.
AU - Iqbal, Javeed
N1 - Publisher Copyright:
© 2019 American Society of Hematology. All rights reserved.
PY - 2019/12/12
Y1 - 2019/12/12
N2 - 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 5 .03). The IHC algorithm classification showed high interobserver reproducibility among pathologists and was validated in a second PTCL-NOS cohort (n 5 124), where a significant difference in OS between the PTCL-GATA3 and PTCL-TBX21 subtypes was confirmed (P 5 .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 5 .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 CD81 cytotoxic phenotype in the PTCL-TBX21 subtype (P 5 .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.
AB - 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 5 .03). The IHC algorithm classification showed high interobserver reproducibility among pathologists and was validated in a second PTCL-NOS cohort (n 5 124), where a significant difference in OS between the PTCL-GATA3 and PTCL-TBX21 subtypes was confirmed (P 5 .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 5 .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 CD81 cytotoxic phenotype in the PTCL-TBX21 subtype (P 5 .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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U2 - 10.1182/blood.2019000779
DO - 10.1182/blood.2019000779
M3 - Article
C2 - 31562134
AN - SCOPUS:85076253508
SN - 0006-4971
VL - 134
SP - 2159
EP - 2170
JO - Blood
JF - Blood
IS - 24
ER -