Quantitative Cyclin D1 Expression Is a Prognostic Indicator in Patients with Mantle Cell Lymphoma.
Alexa Siddon, Richard Torres, Henry Rinder, Brian Smith, John Howe, Christopher Tormey. Yale University School of Medicine, New Haven, CT
Background: Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm comprising between 3-10% of all non-Hodgkin lymphomas. With advances in therapy regimens, the median survival in patients with MCL is 4-5 years. The hallmark of this disease is the t(11;14)(q13;32) translocation. While the B-cell immunophenotype of MCL has classically been described as CD19+, CD20+, CD5+, CD10-, CD23- and FMC7+ several variants have been described including CD23+ MCL. Molecular testing for t(11;14) by fluorescence in situ hybridization or cyclin D1 immunohistochemistry is generally used to establish the diagnosis of MCL. The aim of this study is to determine whether the alternate technique of quantitative cyclin D1 mRNA expression correlates with patient survival or B-cell immunophenotype by flow cytometry.
Design: Peripheral blood or bone marrow was analyzed using either 4 or 6-color flow cytometry; the B cells were interrogated for a spectrum of markers including CD19, CD20, CD5, CD23, and CD43. Specimens from patients with CD19+ CD5+ monoclonal disease suspicious for MCL (n=40) were analyzed for overexpression of cyclin D1 mRNA by real-time quantitative PCR. Cyclin D1 mRNA concentration was determined by normalizing the PCR cycle threshold to that of CD19 mRNA. Survival was measured in months following the initial cyclin D1 analysis.
Results: The largest difference in overall patient survival was found at a cyclin D1 level of 75.
Median survival for patients with high cyclin D1 levels was 36 months versus an undefined average survival in patients with low cyclin D1 levels (p=0.0286). There is no correlation between numbers of CD19+ CD5+ lymphocytes in peripheral blood and the level of cyclin D1. There was no difference in average cyclin D1 expression in patients with CD23+ MCL versus patients with CD23- MCL. There was also no difference in survival in these patient groups.
Conclusions: Quantitative cyclin D1 mRNA is a valuable prognostic indicator in patients with MCL. The level of cyclin D1 expression does not correlate with immunophenotypic disease variants such as CD23+ MCL.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 195, Wednesday Afternoon