title: Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan.
abstract: Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium- to large-sized cells in 13 cases (65%), small- to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2(+) (60%), CD3ɛ(+) (100%), CD4(+) (10%), CD7(+) (95%), CD8(+) (80%), CD56(+) (85%), TIA-1(+) (100%), Granzyme B(+) (25%), T-cell receptor (TCR)β(+) (10%), TCRγ(+) (35%), TCRγδ(+) (50%), and double negative for TCR (six cases, 30%). All cases were EBER(-). The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8(+) CD56(+) phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells.
authors.affiliation: Department of Pathology, Tokai University, School of Medicine, Isehara, Japan.
authors.forename: Sakura
authors.initials: S
authors.lastname: Tomita
authors.affiliation: Department of Pathology, Tokai University, School of Medicine, Isehara, Japan.
authors.forename: Yara Y
authors.initials: YY
authors.lastname: Kikuti
authors.affiliation: Department of Pathology, Tokai University, School of Medicine, Isehara, Japan.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Carreras
authors.affiliation: Department of Hematology, Tokai University, School of Medicine, Isehara, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Department of Hematology, Tokai University, School of Medicine, Isehara, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Oncology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Takasaki
authors.affiliation: Department of Oncology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Sakai
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Department of Pathology and Hematopathology Unit, Hospital Clinic Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bea
authors.affiliation: Department of Pathology and Hematopathology Unit, Hospital Clinic Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Elias
authors.identifier: http://orcid.org/0000-0001-9850-9793
authors.initials: E
authors.lastname: Campo
authors.affiliation: Department of Pathology, Tokai University, School of Medicine, Isehara, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D055028:Comparative Genomic Hybridization; D058527:Enteropathy-Associated T-Cell Lymphoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D005260:Female; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis