Nuclear Expression of the Sox 11 Transcription Factor in Mantle Cell Lymphoma, and Cytoplasmic Expression in Follicular Lymphoma and Multiple Myeloma: Pathogenetic Implications.

Abstract 2925 Poster Board II-901 Mantle cell lymphoma (MCL) is characterized by nuclear cyclin D1 expression resulting from the t(11;14)(q13;q32). As cyclin D1 overexpression alone is insufficient for B-cell transformation, we have investigated other potentially contributing mutations. Sox11 is a member of a large family of transcription factors containing a DNA-binding high-mobility group (HMG) domain and shares homology with Sox4, which is involved in lymphopoiesis. Recent reports have identified Sox11 expression in the majority of MCL, suggesting it may contribute to pathogenesis (Ek et al, Blood 2008;111:800; Wang et al, Br J Haematol 2008;143:248). Methods: Patients with MCL diagnosed at the Univ. of Virginia from 1997-2008 and for whom nodal, marrow or spleen tissue blocks were available were identified from the Pathology database. Follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), hairy cell leukemia (HCL) and multiple myeloma (MM) were also analyzed. Formalin-fixed, paraffin-embedded samples were stained by immunohistochemistry for cyclinD1, Sox11 (rabbit a/Sox11, 1:100, Sigma) and Ki-67. Nuclear and/or cytoplasmic expression was determined by two of us (YT, JC). Results: All MCL samples revealed nuclear cyclin D1 expression. Nuclear but not cytoplasmic Sox11 expression was identified in all 24 non-blastoid and in 5/6 blastoid samples; 1 blastoid sample showed only cytoplasmic Sox11 staining (Table). Four of 5 HCL expressed cyclin D1 but were negative for Sox11; 4/5 MM also were cyclin D1-positive, with 3 positive for cytoplasmic Sox11 including 2 of the cyclin D1-positive cases. All 5 FL showed cytoplasmic Sox11 positivity, whereas all MZL and SLL were negative for cytoplasmic or nuclear staining. | Type | Patients | Samples | Nuclear Cyclin D1+ | Nuclear Sox11+ | Cytoplasmic Sox11+ | |:------------------:| -------- | ------- | ------------------ | -------------- | ------------------ | | MCL, non –blastoid | 22 | 24 | 24 | 24 | | | MCL, blastoid | 5 | 6 | 6 | 5 | 1 | | FL | 5 | 5 | N.D.[1][1] | | 5 | | MZL | 6 | 6 | | | | | SLL | 6 | 6 | | | | | HCL[2][2] | 5 | 5 | 4 | | | | MM[3][3] | 5 | 5 | 4 | | 3 | * [↵][4]1 N.D. = Not Done * [↵][5]2 3 spleen, 2 bone marrow samples * [↵][6]3 Bone marrow samples Conclusions: Nuclear Sox11 expression was uniformly identified in MCL, with the exception of cytoplasmic expression in a single blastoid case. No nuclear Sox11 was present in HCL or MM despite the expression of cyclin D1, although 3 MM showed cytoplasmic Sox11 staining. These findings suggest that nuclear Sox11 overexpression is not a direct result of dysregulated cyclin D1 signaling but instead occurs by alternative mechanisms. The significance of cytoplasmic staining remains uncertain. A potential pathogenetic role for Sox11 and possibly other Sox family transcription factors warrants further investigation in MCL and other lymphoproliferative neoplasms for diagnostic use and therapeutic targeting. Disclosures: No relevant conflicts of interest to declare. [1]: #fn-1 [2]: #fn-2 [3]: #fn-3 [4]: #xref-fn-1-1 [5]: #xref-fn-2-1 [6]: #xref-fn-3-1