title: Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype.
abstract: Mantle cell lymphoma is a mature lymphoid neoplasm characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. SOX11 is a transcription factor commonly overexpressed in these tumors but absent in most other mature B-cell lymphomas whose function is not well understood. Experimental studies have shown that silencing of SOX11 in mantle cell lymphoma cells promotes the shift from a mature B cell into an early plasmacytic differentiation phenotype, suggesting that SOX11 may contribute to tumor development by blocking the B-cell differentiation program. The relationship between SOX11 expression and terminal B-cell differentiation in primary mantle cell lymphoma and its relationship to the plasmacytic differentiation observed in occasional cases is not known. In this study we have investigated the terminal B-cell differentiation phenotype in 60 mantle cell lymphomas, 41 SOX11-positive and 19 SOX11-negative. Monotypic plasma cells and lymphoid cells with plasmacytic differentiation expressing cyclin D1 were observed in 7 (37%) SOX11-negative but in none of 41 SOX11-positive mantle cell lymphomas (P<0.001). Intense cytoplasmic expression of a restricted immunoglobulin light chain was significantly more frequent in SOX11-negative than -positive tumors (58 vs 13%) (P=0.001). Similarly, BLIMP1 and XBP1 expression was also significantly more frequent in SOX11-negative than in -positive cases (83 vs 34% and 75 vs 11%, respectively) (P=0.001). However, no differences in the expression of IRF4/MUM1 were observed among these subtypes of mantle cell lymphoma. In conclusion, these results indicate that SOX11-negative mantle cell lymphoma may be a particular subtype of this tumor characterized by more frequent morphological and immunophenotypic terminal B-cell differentiation features that may be facilitated by the absence of SOX11 transcription factor.
authors.affiliation: Hematopathology Unit, Department of Anatomic Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain.|Hospital Nostra Senyora de Meritxell, Escaldes-Engordany, Principat d'Andorra.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ribera-Cortada
authors.affiliation: Hematopathology Unit, Department of Anatomic Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinez
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Amador
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Royo
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Beà
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Department of Hematology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gine
authors.affiliation: Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.affiliation: Department of Pathology, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano
authors.affiliation: Department of Histopathology, Royal Marsden Hospital, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wotherspoon
authors.affiliation: Hematopathology Unit, Department of Anatomic Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.affiliation: Hematopathology Unit, Department of Anatomic Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Hematopathology Unit, Department of Anatomic Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D020522:Lymphoma, Mantle-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology*; D055751:SOXC Transcription Factors / Q000096:biosynthesis* / Q000276:immunology
chemical_list: C097473:SOX11 protein, human; D055751:SOXC Transcription Factors