Correlation of cyclin D1 transcript levels, transcript type and protein expression with proliferation and histology among mantle cell lymphoma

Background: Cyclin D1 expression is central to mantle cell lymphoma (MCL) biology. The cyclin D1 gene produces two forms of mRNA: long (D1L) and short (D1S) versions. Aims: To study the relationship between histology, cyclin D1 mRNA (transcript) levels, cyclin D1 transcript type, cyclin D1 protein expression by immunohistochemistry (IHC), and proliferation (Ki-67%). Methods: 17 MCLs were initially studied for: levels of expression of cyclin D1 transcripts and for cyclin D1 transcript type by reverse-transcriptase PCR; intensity and percentage cyclin D1 protein expression by IHC; and Ki-67% by IHC. The relationship between cyclin D1 protein expression and proliferation was further validated on an independent set of 23 MCLs. Results: MCLs expressed variable levels of cyclin D1 at both transcript and protein levels. Furthermore, D1L and D1S were the predominant transcripts in 69% and 31% of cases, respectively. While only 9% of cases with dominance of D1L had blastoid histology, 60% of the cases with dominance of the D1S had blastoid features. Furthermore, the levels of D1L showed direct correlation with cyclin D1 protein expression and Ki-67%. Among these cases, and in the independent set of MCLs (n=40), the level of cyclin D1 protein expression directly correlated with Ki-67%. Conclusions: MCLs express variable levels of cyclin D1 transcripts and protein, and have variable proliferation (Ki-67%). Cases with dominance of D1S transcripts are more likely to be of blastoid morphology. There is correlation between D1L transcripts levels, cyclin D1 protein expression and Ki-67%.