Cyclin D1-negative Mantle Cell Lymphoma: A Clinicopathological Study Based on Gene Expression Profiling

Cyclin D1 overexpression is believed to be essential in the pathogenesis of mantle cell lymphoma (MCL). Hence, the existence of cyclin D1-negative MCL has been controversial and difficult to substantiate. Our previous gene expression profiling study identified several cases which lacked cyclin D1 expression, but had a gene expression signature typical of MCL. Herein, we report the clinical, pathologic, and genetic features of six cases of cyclin D1-negative MCL. All six cases exhibited the characteristic morphologic features and the unique gene expression signature of MCL, but lacked the t(11;14)(q13;q32) by FISH analysis. The tumor cells also failed to express cyclin D1 protein, but instead expressed either cyclin D2 (two cases) or cyclin D3 (four cases). There was good correlation between cyclin D protein expression and the corresponding mRNA expression levels by gene expression analysis. Using interphase FISH, we did not detect chromosomal translocations or amplifications involving the CCND2 and CCND3 loci in these cases. Patients with cyclin D1-negative MCL were similar clinically to those with cyclin D1-positive MCL. In conclusion, cases of cyclin D1negative MCL do exist and are part of the spectrum of MCL. Up-regulation of cyclin D2 or D3 may substitute for cyclin D1 in the pathogenesis of MCL. only. For personal use at PENN STATE UNIVERSITY on February 23, 2013. bloodjournal.hematologylibrary.org From