期刊
BLOOD
卷 134, 期 24, 页码 2159-2170出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2019000779
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资金
- National Institutes of Health National Cancer Institute [UH2/UH31UH2CA206127, STTR 1R41CA221466, POI 1P01CA229100]
- National Cancer Institute Eppley Cancer Center Support grant [P30CA036727]
- National Cancer Institute Specialized Program of Research Excellence (SPORE) [2P50CA107399-11A1]
- City of Hope Cancer Center Support grant [P30 CA033572]
- National Cancer Institute [P50 CA97274]
- Singapore Ministry of Health's National Medical Research Council
- Tanoto Foundation
- New Century Foundation Pte Ltd
- Ling Foundation
- Singapore National Cancer Centre Research Fund
- Oncology Academic Clinical Program (ONCO ACP) Cancer Collaborative Scheme
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 (PTCLNOS). 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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