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: Inmaculada Ribera-Cortada, Daniel Martinez, Virginia Amador, Cristina Royo, Alba Navarro, Silvia Beà, Eva Gine, Laurence de Leval, Sergio Serrano, Andrew Wotherspoon, Dolors Colomer, Antonio Martinez, Elías Campo
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 28 Issue 11 Pg. 1435-47 (Nov 2015) ISSN: 1530-0285 [Electronic] United States
• PMID: 26360498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SOX11 protein, human
• SOXC Transcription Factors

Topics

• Adult
• Aged
• Aged, 80 and over
• B-Lymphocytes (pathology)
• Cell Differentiation
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lymphoma, Mantle-Cell (immunology, metabolism, pathology)
• Male
• Middle Aged
• Plasma Cells (pathology)
• SOXC Transcription Factors (biosynthesis, immunology)