title: PML nuclear bodies and SATB1 are associated with HLA class I expression in EBV+ Hodgkin lymphoma.
abstract: Tumor cells of classical Hodgkin lymphoma (cHL) are characterized by a general loss of B cell phenotype, whereas antigen presenting properties are commonly retained. HLA class I is expressed in most EBV+ cHL cases, with an even enhanced expression in a proportion of the cases. Promyelocytic leukemia protein (PML) and special AT-rich region binding protein 1 (SATB1) are two global chromatin organizing proteins that have been shown to regulate HLA class I expression in Jurkat cells. We analyzed HLA class I, number of PML nuclear bodies (NBs) and SATB1 expression in tumor cells of 54 EBV+ cHL cases and used 27 EBV- cHL cases as controls. There was a significant difference in presence of HLA class I staining between EBV+ and EBV- cases (p<0.0001). We observed normal HLA class I expression in 35% of the EBV+ and in 19% of the EBV- cases. A stronger than normal HLA class I expression was observed in approximately 40% of EBV+ cHL and not in EBV- cHL cases. 36 EBV+ cHL cases contained less than 10 PML-NBs per tumor cell, whereas 16 cases contained more than 10 PML-NBs. The number of PML-NBs was positively correlated to the level of HLA class I expression (p<0.01). The percentage of SATB1 positive cells varied between 0% to 100% in tumor cells and was inversely correlated with the level of HLA class I expression, but only between normal and strong expression (p<0.05). Multivariable analysis indicated that the number of PML-NBs and the percentage of SATB1+ tumor cells are independent factors affecting HLA class I expression in EBV+ cHL. In conclusion, both PML and SATB1 are correlated to HLA class I expression levels in EBV+ cHL.
authors.affiliation: Department of Pathology & Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.forename: Rianne
authors.initials: R
authors.lastname: Veenstra
authors.forename: Bea
authors.initials: B
authors.lastname: Rutgers
authors.forename: Ilja
authors.initials: I
authors.lastname: Nolte
authors.forename: Gustaaf
authors.initials: G
authors.lastname: van Imhoff
authors.forename: Lydia
authors.initials: L
authors.lastname: Visser
authors.forename: Arjan
authors.initials: A
authors.lastname: Diepstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006689:Hodgkin Disease / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015395:Histocompatibility Antigens Class I; D036961:Matrix Attachment Region Binding Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; C076189:SATB1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human