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.


OBJECTIVE
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%.
Department of Histopathology, Hammersmith Hospital & Imperial College, London, UK.
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R
Shakir
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Ngo
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Naresh
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019938:Cyclin D1