Aberrant Expression of CD10 and BCL6 in Mantle Cell Lymphoma

Abstract

Aims

Mantle cell lymphoma (MCL) is characterized by distinctive histologic and molecular features. Aberrant expression of BCL6 and CD10 has occasionally been reported, but the biological features of such cases are largely unknown. This study aimed to define the epidemiologic, histologic and cytogenetic characteristics of BCL6 and CD10-positive MCLs, also investigating possible biological features.

Methods and Results

165 cases of cyclin D1 and t(11;14)(q13;q34) positive MCLs were studied for CD10 and BCL6 immunohistochemical expression which was documented in 26/165 (15.8%) cases (BCL6 17/165; CD10 11/165; BCL6 and CD10 co-expression 2/165). CD10-positivity was significantly more frequent in females (63.3%; p<0.01). Either expression significantly correlated with higher mean proliferation index and higher prevalence of MUM1 positivity (p<0.05). Fluorescence in situ hybridization (FISH) for BCL6 (3q27) gene derangements was performed on the BCL6 and CD10-positive cases and 98 matched controls: amplifications were more frequently documented in BCL6-positive than BCL6-negative cases (50.0% versus 19.4% of cases) (p<0.05). The mutational status of the variable immunoglobulin heavy chain genes (IGVH) was investigated by Sanger sequencing: 5 of the 6 successfully tested cases (83.3%) showed no somatic hyper-mutations.

Conclusions

Aberrant CD10 and BCL6 expression defines a subset of MCLs with higher mean Ki67 index and higher prevalence of MUM1 expression. BCL6 protein positivity correlates with cytogenetic aberrations involving the BCL6 gene. Though successfully examined in few cases, the high prevalence of un-mutated IGVH genes points at a pre-germinal cell origin also for these phenotypically aberrant cases.

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