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

Abstract

Aims: 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. We aimed to study the relationship between: 1) histology 2) cyclin D1 mRNA (transcript) levels 3) cyclin D1 transcript type 4) cyclin D1 protein expression by immunohistochemistry (IHC) 5) proliferation (Ki-67%).

Methods: We initially studied 17 MCLs for: a) levels of expression cyclin D1 transcripts and for cyclin D1 transcript type by reverse-transcriptase polymerase chain reaction, b) intensity and percentage cyclin D1 protein expression by IHC, and c) Ki-67% by IHC. Relationship between cylcin D1 protein expression and proliferation was further validated on an independent set of 23 MCLs.

Results: MCLs expressed variable levels of cyclin D1 both at transcript and protein levels. Furthermore, D1L and D1S were the predominant transcripts in 69% and 31% 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. Further, 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. We also show correlation between D1L transcripts levels, cyclin D1 protein expression and Ki-67%.