title: Clinicopathologic Analysis of Angioimmunoblastic T-cell Lymphoma With or Without RHOA G17V Mutation Using Formalin-fixed Paraffin-embedded Sections.
abstract: Angioimmunoblastic T-cell lymphoma (AITL) is an infrequent subtype of peripheral T-cell lymphoma derived from follicular helper T cells. Recently, a somatic G17V RHOA gene mutation has been reported. In this article, we examined the RHOA G17V mutation in 18 cases of AITL by 3 different techniques of Sanger sequencing, fully automated SNP genotyping, and deep sequencing, using routine diagnostic formalin-fixed paraffin-embedded tissue. The RHOA G17V mutation was detected in 10 cases (56%). Among the 10 mutated cases, 8 cases were detected by all 3 methods. The status of RHOA mutation was subsequently compared with the clinicopathologic characteristics of AITL. RHOA-mutated AITL (10 cases) was clinically characterized by high serum IL-2R and a poor ECOG performance status. By immunohistochemistry, expression of CD10, PD-1, CXCL13, and CCR4 and a wide distribution of CD21(+) follicular dendritic cells were observed in RHOA-mutated cases. Among these, CCR4 expression and the CD21(+) network in RHOA-mutated AITL cases were more extensive than in the RHOA mutation-negative AITL cases (P<0.05). Thus, RHOA-mutated AITL cases are more characteristic of follicular helper T cells, and the presence of such a mutation is an important marker for AITL.
authors.affiliation: Departments of *Pathology †Laboratory Medicine ‡Hematology/Oncology, Tokai University School of Medicine, Isehara §Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Nagao
authors.forename: Yara Yukie
authors.initials: YY
authors.lastname: Kikuti
authors.forename: Joaquim
authors.initials: J
authors.lastname: Carreras
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Miyaoka
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Matsushita
authors.forename: Minoru
authors.initials: M
authors.lastname: Kojima
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Mamiko
authors.initials: M
authors.lastname: Sakata-Yanagimoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D005557:Formaldehyde; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D016707:Tissue Fixation; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C066737:RHOA protein, human; D005557:Formaldehyde; D020742:rhoA GTP-Binding Protein