Cyclin D1 (CCND1) messenger RNA expression as assessed by real-time PCR contributes to diagnosis and follow-up control in patients with mantle cell lymphoma

Molecular diagnosis of mantle cell lymphoma (MCL) can be difficult because the t(11;14)/IGH@-CCND1 is extremely heterogeneous at the DNA level. Aiming to establish a reliable molecular tool that could be easily implemented in routine diagnostics, we developed a new real-time polymerase chain reaction (PCR) assay for CCND1 expression measurement and evaluated 451 cases: 142 MCL, 76 chronic lymphocytic leukemia, 20 hairy cell leukemia, 13 hairy cell leukemia-variant, 20 splenic marginal zone lymphoma, 91 other mature B-cell neoplasms, 29 other hematologic neoplasms, and 60 healthy individuals. Sensitivity of the real-time PCR assay was up to 10−4. In t(11;14)/IGH@-CCND1 positive lymphoma samples (n = 150), median %CCND1/ABL1 expression level was 178.2 (range: 1.5–4, 152.0). Normalized by t(11;14)/IGH@-CCND1 positive cells as determined by fluorescence in situ hybridization IGH@-CCND1 positive samples showed a median %CCND1/ABL1 of 445.8 (range: 17.9–4,848.5). A normalized %CCND1/ABL1 expression of at least 17.0 was chosen as threshold for CCND1 positivity. For unnormalized samples, the positive detection rate of t(11;14)/IGH@-CCND1 by CCND1 expression was 87.3%. Healthy individuals had low %CCND1/ABL1 (median, 1.1; range, 0.0–7.8). The negative predictive value for exclusion of a t(11;14)/IGH@-CCND1 by CCND1 expression was 95.3% by the above threshold. %CCND1/ABL1 was higher in MCL than in the remaining B-cell lymphomas (mean ± SD, 392.9 ± 685.3 vs. 46.0 ± 305.0; p < 0.001). In 66 follow-up samples, CCND1 showed 2.5–3.5 log reduction after chemotherapy and increase at relapse. CCND1 expression could serve as adjunct to other techniques in diagnosis and follow-up of B-cell lymphomas.