PMID- 27775850 OWN - NLM STAT- MEDLINE DCOM- 20170613 LR - 20220409 IS - 1365-2559 (Electronic) IS - 0309-0167 (Linking) VI - 70 IP - 4 DP - 2017 Mar TI - Clinicopathological characteristics and genomic profile of primary sinonasal tract diffuse large B cell lymphoma (DLBCL) reveals gain at 1q31 and RGS1 encoding protein; high RGS1 immunohistochemical expression associates with poor overall survival in DLBCL not otherwise specified (NOS). PG - 595-621 LID - 10.1111/his.13106 [doi] AB - 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 RNAs (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) (GSE11318, 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 (CKS1B), -6q26 (PARK2), +8q24.21 (MYC), -9p21.3 (MTAP, CDKN2A/B), -17p13.1 (TP53) and +18q21.33 (BCL2) with 82-91% agreement. Minimal common regions included biologically relevant genes of MNDA (+1q23.1), RGS1 and RGS13 (+1q31.2), FOXP1 (+3p13), PRDM1 (BLIMP1) and PARK2 (-6q21q26), MYC (+8q24.21), CDKN2A (-9p21.3), PTEN (-10q23.31), MDM2 (+12q15), TP53 (-17p13.1) and BCL2 (+18q21.33). Correlation between DNA copy number and protein immunohistochemistry was confirmed for RGS1, RGS13, FOXP1, PARK2 and BCL2. The microenvironment had high infiltration of M2-like tumour associated macrophages (TAMs) and CD8(+) T lymphocytes that associated with higher genomic instability. The DLBCL(sn) validation set confirmed the clinicopathological characteristics, all FISH loci and immunohistochemistry (IHC) for RGS1. RGS1, one of the most frequently altered genes, was analysed by IHC in DLBCL(all) and high RGS1 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 RGS1 IHC expression associates with poor overall survival in DLBCL(all ()(NOS)()) . CI - (c) 2016 John Wiley & Sons Ltd. FAU - Carreras, Joaquim AU - Carreras J AD - Department of Pathology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Kikuti, Yara Y AU - Kikuti YY AD - Department of Pathology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Bea, Silvia AU - Bea S AD - Hematopathology Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. FAU - Miyaoka, Masashi AU - Miyaoka M AD - Department of Pathology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Hiraiwa, Shinichiro AU - Hiraiwa S AD - Department of Pathology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Ikoma, Haruka AU - Ikoma H AD - Department of Pathology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Nagao, Ryoko AU - Nagao R AD - Department of Pathology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Tomita, Sakura AU - Tomita S AD - Department of Pathology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Martin-Garcia, David AU - Martin-Garcia D AD - Hematopathology Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. FAU - Salaverria, Itziar AU - Salaverria I AD - Hematopathology Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. FAU - Sato, Ai AU - Sato A AD - Department of Hematology and Oncology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Ichiki, Akifumi AU - Ichiki A AD - Department of Hematology and Oncology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Roncador, Giovanna AU - Roncador G AD - Monoclonal Antibodies Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. FAU - Garcia, Juan F AU - Garcia JF AD - Department of Pathology, MD Anderson Cancer Center Madrid, Madrid, Spain. FAU - Ando, Kiyoshi AU - Ando K AD - Department of Hematology and Oncology, Tokai University, School of Medicine, Kanagawa, Japan. FAU - Campo, Elias AU - Campo E AD - Hematopathology Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. FAU - Nakamura, Naoya AU - Nakamura N AD - Department of Pathology, Tokai University, School of Medicine, Kanagawa, Japan. LA - eng PT - Journal Article DEP - 20170109 PL - England TA - Histopathology JT - Histopathology JID - 7704136 RN - 0 (Biomarkers, Tumor) RN - 0 (RGS Proteins) RN - 0 (RGS1 protein, human) SB - IM MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/analysis MH - Chromosomes, Human, Pair 1/*genetics MH - Female MH - Gene Dosage MH - Gene Expression Profiling MH - Humans MH - Image Processing, Computer-Assisted MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Loss of Heterozygosity MH - Lymphoma, Large B-Cell, Diffuse/*genetics/mortality/*pathology MH - Male MH - Middle Aged MH - Oligonucleotide Array Sequence Analysis MH - Prognosis MH - RGS Proteins/*genetics MH - Transcriptome OTO - NOTNLM OT - DNA copy number changes OT - FISH technique OT - RGS1 OT - digital image quantification OT - immunohistochemistry OT - prognosis OT - sinonasal diffuse large B cell lymphoma (DLBCL) OT - tumour microenvironment EDAT- 2016/10/25 06:00 MHDA- 2017/06/14 06:00 CRDT- 2016/10/25 06:00 PHST- 2016/06/08 00:00 [received] PHST- 2016/09/29 00:00 [revised] PHST- 2016/10/21 00:00 [accepted] PHST- 2016/10/25 06:00 [pubmed] PHST- 2017/06/14 06:00 [medline] PHST- 2016/10/25 06:00 [entrez] AID - 10.1111/his.13106 [doi] PST - ppublish SO - Histopathology. 2017 Mar;70(4):595-621. doi: 10.1111/his.13106. Epub 2017 Jan 9.