Oncotarget

Research Papers:

Overlap at the molecular and immunohistochemical levels between angioimmunoblastic T-cell lymphoma and a subgroup of peripheral T-cell lymphomas without specific morphological features

Rebeca Manso, Julia González-Rincón, Manuel Rodríguez-Justo, Giovanna Roncador, Sagrario Gómez, Margarita Sánchez-Beato, Miguel A. Piris and Socorro M. Rodríguez-Pinilla _

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Oncotarget. 2018; 9:16124-16133. https://doi.org/10.18632/oncotarget.24592

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Abstract

Rebeca Manso1, Julia González-Rincón2,5, Manuel Rodríguez-Justo3, Giovanna Roncador4, Sagrario Gómez2, Margarita Sánchez-Beato2, Miguel A. Piris1,5 and Socorro M. Rodríguez-Pinilla1,5

1Pathology Department, Fundación Jiménez Díaz, UAM, Madrid, Spain

2Instituto Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHIM), Madrid, Spain

3UCL Cancer Institute, Department of Research Pathology, London, UK

4Monoclonal Antibodies Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

5Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain

Correspondence to:

Socorro M. Rodríguez-Pinilla, email: smrodriguez@fjd.es

Keywords: AITL; PTCL; TFH-phenotype; IHQ; NGS

Received: August 02, 2017     Accepted: February 21, 2018     Epub: March 01, 2018      Published: March 23, 2018

ABSTRACT

The overlap of morphology and immunophenotype between angioimmunoblastic T-cell lymphoma (AITL) and other nodal peripheral T-cell lymphomas (n-PTCLs) is a matter of current interest whose clinical relevance and pathogenic background have not been fully established. We studied a series of 98 n-PTCL samples (comprising 57 AITL and 41 PTCL-NOS) with five TFH antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS), looked for mutations in five of the genes most frequently mutated in AITL (TET2, DNMT3A, IDH2, RHOA and PLCG1) using the Next-Generation-Sequencing Ion Torrent platform, and measured the correlations of these characteristics with morphology and clinical features. The percentage of mutations in the RHOA and TET2 genes was similar (23.5% of cases). PLCG1 was mutated in 14.3%, IDH2 in 11.2% and DNMT3A in 7.1% of cases, respectively. In the complete series, mutations in RHOA gene were associated with the presence of mutations in IDH2, TET2 and DNMT3A (p < 0.001, p = 0.043, and p = 0.029, respectively). Fourteen cases featured RHOA mutations without TET2 mutations. A close relationship was found between the presence of these mutations and a TFH-phenotype in AITL and PTCL-NOS patients. Interestingly, BCL-6 expression was the only TFH marker differentially expressed between AITL and PTCL-NOS cases. There were many fewer mutated cases than there were cases with a TFH phenotype. Overall, these data suggest alternative ways by which neoplastic T-cells overexpress these proteins. On the other hand, no clinical or survival differences were found between any of the recognized subgroups of patients with respect to their immunohistochemistry or mutational profile.


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