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

J Clin Pathol. 2008 Aug;61(8):920-7. doi: 10.1136/jcp.2008.057455. Epub 2008 Jun 13.

Abstract

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%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Humans
  • Ki-67 Antigen / metabolism
  • Lymphoma, Mantle-Cell / genetics
  • Lymphoma, Mantle-Cell / metabolism*
  • Lymphoma, Mantle-Cell / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Transcription, Genetic

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Cyclin D1