Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan View Full Text


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Article Info

DATE

2015-07-31

AUTHORS

Sakura Tomita, Yara Y Kikuti, Joaquim Carreras, Minoru Kojima, Kiyoshi Ando, Hirotaka Takasaki, Rika Sakai, Katsuyoshi Takata, Tadashi Yoshino, Silvia Bea, Elias Campo, Naoya Nakamura

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. More... »

PAGES

1286-1296

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.2015.85

DOI

http://dx.doi.org/10.1038/modpathol.2015.85

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043960689

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26226842


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26 schema:description 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.
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33 schema:keywords Asia
34 CD4
35 CD56
36 CD7
37 CD8
38 Cd2
39 EATL
40 EATL type II
41 Europe
42 Japan
43 TCR
44 TIA-1
45 Western countries
46 appearance
47 array comparative genomic hybridization
48 cases
49 celiac disease
50 cell lymphoma
51 cell origin
52 cell receptor
53 cells
54 changes
55 comparative genomic hybridization
56 copy number gains
57 correlation
58 countries
59 cytotoxic CD8
60 de novo
61 different loci
62 digestive tract
63 disease
64 enteropathy
65 fish
66 fluorescence
67 formalin
68 frequent changes
69 gain
70 genomic hybridization
71 genomic profiles
72 good correlation
73 granzyme
74 high-resolution oligonucleotide microarrays
75 histological appearance
76 homogeneous series
77 hybridization
78 immunohistochemical profile
79 immunohistochemistry
80 immunophenotype
81 large-sized cells
82 loci
83 loss
84 lymphoma
85 medium
86 medium-sized cells
87 microarrays
88 more similarities
89 northern Europe
90 novo
91 number gain
92 oligonucleotide microarrays
93 origin
94 paraffin-embedded sections
95 pathogenesis
96 patients
97 phenotype
98 predominance
99 profile
100 receptors
101 recurrent copy number gains
102 sections
103 series
104 similarity
105 situ hybridization
106 tract
107 type I
108 type II
109 world
110 αβ
111 γδ
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