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

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 a...

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Bibliographic Details
Published in:Blood 2019-12, Vol.134 (24), p.2159-2170
Main Authors: Amador, Catalina, Greiner, Timothy C., Heavican, Tayla B., Smith, Lynette M., Galvis, Karen Tatiana, Lone, Waseem, Bouska, Alyssa, D'Amore, Francesco, Pedersen, Martin Bjerregaard, Pileri, Stefano, Agostinelli, Claudio, Feldman, Andrew L., Rosenwald, Andreas, Ott, German, Mottok, Anja, Savage, Kerry J., de Leval, Laurence, Gaulard, Philippe, Lim, Soon Thye, Ong, Choon Kiat, Ondrejka, Sarah L., Song, Joo, Campo, Elias, Jaffe, Elaine S., Staudt, Louis M., Rimsza, Lisa M., Vose, Julie, Weisenburger, Dennis D., Chan, Wing C., Iqbal, Javeed
Format: Article
Language:English
Subjects:
Adult
Aged
Algorithms
Biomarkers, Tumor
Computational Biology - methods
Female
Gene Expression Profiling
Humans
Immunohistochemistry
Immunophenotyping
Lymphoid Neoplasia
Lymphoma, T-Cell, Peripheral - diagnosis
Lymphoma, T-Cell, Peripheral - etiology
Lymphoma, T-Cell, Peripheral - metabolism
Male
Middle Aged
Neoplasm Staging
Prognosis
Reproducibility of Results
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Summary: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. •Two novel prognostic PTCL subtypes (PTCL-GATA3 and PTCL-TBX21) were classified using an IHC algorithm applicable to routine clinical practice.•Distinct morphological and immunophenotypic features of 2 novel PTCL subtypes were identified. [Display omitted]
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.2019000779