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Clinicopathological characteristics and genomic profile of primary sinonasal tract diffuse large B cell lymphoma ( DLBCL ) reveals gain at 1q31 and RGS 1 encoding protein; high RGS 1 immunohistochemical expression associates with poor overall survival in DLBCL not otherwise specified ( NOS )
Author(s) -
Carreras Joaquim,
Kikuti Yara Y,
Beà Sílvia,
Miyaoka Masashi,
Hiraiwa Shinichiro,
Ikoma Haruka,
Nagao Ryoko,
Tomita Sakura,
MartinGarcia David,
Salaverria Itziar,
Sato Ai,
Ichiki Akifumi,
Roncador Giovanna,
Garcia Juan F,
Ando Kiyoshi,
Campo Elias,
Nakamura Naoya
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13106
Subject(s) - fluorescence in situ hybridization , diffuse large b cell lymphoma , cdkn2a , biology , comparative genomic hybridization , pten , cancer research , microbiology and biotechnology , lymphoma , gene , genetics , chromosome , immunology , apoptosis , pi3k/akt/mtor pathway
Aims We aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large B cell lymphoma ( DLBCL sn ) in a series of 240 cases of DLBCL not otherwise specified [ DLBCL all ( NOS ) ], including DLBCL sn training set ( n = 11) and validation set ( n = 18), and DLBCL non‐sn ( n = 211). Methods and results In the training set, 82% had a non‐germinal center B‐cell‐like (Hans’ Classifier) (non‐ GCB ) phenotype and 18% were Epstein–Barr virus‐encoded small RNA s ( EBER ) + . The genomic profile showed gains (+) of 1q21.3q31.2 (55%), 10q24.1 (46%), 11q14.1 (46%) and 18q12.1q23 (46%); losses (−) of 6q26q27 (55%) and 9p21.3 (64%); and copy number neutral loss of heterozygosity (LOH) (acquired uniparental disomy, UPD) at 6p25.3p21.31 (36%). This profile is comparable to DLBCL NOS ( GSE 11318, n = 203.) and closer to non‐ GCB /activated B‐cell‐like subtype ( ABC ). Nevertheless, +1q31, −9p21.3 and −10q11.1q26.2 were more characteristic of DLBCL sn ( P < 0.001). Array results were verified successfully by fluorescence in situ hybridization ( FISH ) on +1q21.3 ( CKS 1B) , −6q26 ( PARK 2 ), +8q24.21 ( MYC ), −9p21.3 ( MTAP , CDKN 2A/B ), −17p13.1 ( TP 53 ) and +18q21.33 ( BCL 2 ) with 82–91% agreement. Minimal common regions included biologically relevant genes of MNDA (+1q23.1), RGS 1 and RGS 13 (+1q31.2), FOXP 1 (+3p13), PRDM1 (BLIMP1) and PARK 2 (−6q21q26) , MYC ( + 8q24.21), CDKN 2A (−9p21.3), PTEN (−10q23.31), MDM 2 (+12q15), TP 53 (−17p13.1) and BCL 2 (+18q21.33). Correlation between DNA copy number and protein immunohistochemistry was confirmed for RGS 1, RGS 13, FOXP 1, PARK 2 and BCL 2. The microenvironment had high infiltration of M2‐like tumour associated macrophages ( TAM s) and CD 8 + T lymphocytes that associated with higher genomic instability. The DLBCL sn validation set confirmed the clinicopathological characteristics, all FISH loci and immunohistochemistry ( IHC ) for RGS 1. RGS 1 , one of the most frequently altered genes, was analysed by IHC in DLBCL all and high RGS 1 expression associated with non‐ GCB , EBER + and unfavourable overall survival (hazard ratio = 1.794; P = 0.016). Conclusions DLBCL sn has a characteristic genomic profile. High RGS 1 IHC expression associates with poor overall survival in DLBCL all ( NOS ) .