Search

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.

Sox11 is a transcription factor involved in embryonic neurogenesis and tissue remodeling. Its role in lymphopoiesis is presently unknown. Recent studies have shown the nuclear expression of sox11 in mantle cell lymphoma, which raises the question about its possible association with t(11;14)(q13;q32), the genetic hallmark of mantle cell lymphoma leading to the overexpression of cyclin D1. In this study, we examined sox11 expression in 211 cases of B-cell neoplasms by immunohistochemistry, and evaluated its association with t(11;14) and overexpression of cyclin D1. Nuclear staining of sox11 was observed in 54 of 57 (95%) mantle cell lymphomas, including 52 of 53 (98%) classical and 2 of 4 variant types. Two of the three mantle cell lymphomas negative for nuclear sox11 staining were analyzed and were positive for t(11;14). All other B-cell lymphomas (114 cases) showed variable positive staining in the cytoplasm, but no nuclear positivity. Sox11 was then examined in plasma cell myeloma and hairy cell leukemia as a subset of plasma cell myeloma carry t(11;14) and overexpress cyclin D1, and cyclin D1 is overexpressed in a subset of hairy cell leukemia independent of t(11;14). We found no nuclear staining of sox11 in 30 plasma cell myelomas examined, including 12 cases with t(11;14)(q13;q32). It is interesting that intense nuclear staining of sox11 was present in a subset of hairy cell leukemias (5 of 10), and was associated with the overexpression of cyclin D1. Our results indicate that the nuclear expression of sox11 is highly associated with mantle cell lymphoma, but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms. Its association with the overexpression of cyclin D1 in hairy cell leukemia suggests that sox11 may be involved in the upregulation of cyclin D1 in this leukemia.