Diagnostic and prognostic implications of tumor expression of the GATA-3 gene in nodal peripheral T-cell lymphoma (nPTCL): Retrospective data from a Latin American cohort.

Autor: de Pádua Covas Lage LA; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FMUSP), Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31/FMUSP), Brazil. Electronic address: luisalberto_lage@yahoo.com.br., Brito CV; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FMUSP), Brazil., Levy D; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FMUSP), Laboratory of Medical Investigation on Immunology & Histocompatibility (LIM-19/FMUSP), Brazil., Culler HF; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FMUSP), Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31/FMUSP), Brazil., Freitas Couto SC; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FMUSP), Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31/FMUSP), Brazil., de Oliveira LBA; Statistical, Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FMUSP), Brazil., Nogueira Zerbini MC; Department of Pathology, Faculty of Medicine, Sao Paulo University (FMUSP), Brazil., Rocha V; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FMUSP), Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31/FMUSP), Brazil; Pró-Sangue Foundation/Sao Paulo Blood Bank, Brazil; Churchill Hospital, Oxford University, UK., Pereira J; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FMUSP), Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology, Non-Hodgkin's Lymphomas and Histiocytic Disorders (LIM-31/FMUSP), Brazil.
Jazyk: angličtina
Zdroj: Leukemia research [Leuk Res] 2022 Mar; Vol. 114, pp. 106794. Date of Electronic Publication: 2022 Feb 01.
DOI: 10.1016/j.leukres.2022.106794
Abstrakt: Background: Nodal peripheral T-cell lymphomas (nPTCL) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in clinical practice. Accurate biomarkers to define the different subtypes of nPTCL and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA-3 gene expression, and its capability to discriminate the different subtypes of nPTCL.
Patients and Methods: We retrospectively assessed GATA-3 gene expression by quantitative real time PCR (qRT-PCR) from neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE) of 80 patients with nPTCL that were admitted in a single cancer treatment center from 2000 to 2017.
Results: Median age was 49 years-old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years, 36.3% were classified as PTCL, NOS, 31.2% as ALK-negative ALCL, 21.2% as ALK-positive ALCL and 11.3% as AITL. The majority of cases had advanced stage cancer (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA-3 gene expression level was 0.49 (range 0 - 7.07) in all cohort, with 0.11 for ALK-positive ALCL, 0.46 for ALK-negative ALCL, 0.86 for PTCL, NOS and 0.67 for AITL. The difference of GATA-3 gene expression among distinct variants of nPTCL was statistically significant (p < 0.001). GATA-3 gene expression levels ≥ 0.71 discriminate PTCL, NOS from ALK-negative ALCL and AITL with sensitivity of 62.0% and specificity of 80.3%. GATA-3 gene expression level ≥ median was associated with poor 2-year OS for PTCL, NOS (46.7% versus 21.4%, p = 0.04) and ALK-negative ALCL (85.7% versus 54.5%, p = 0.04). In multivariate analysis, GATA-3 expression ≥ median was an independent factor associated with poor OS in nPTCL (HR: 2.34, 95% CI: 1.12-4.39, p = 0.041).
Conclusion: GATA-3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL, NOS and ALK-negative ALCL. Moreover, it may also discriminate different subtypes of nPTCL. Further studies with larger series of patients should confirm our findings.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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