title: Expression of cyclin D2 is an independent predictor of the development of hepatic metastasis in colorectal cancer.
abstract: BACKGROUND
  Cyclin D1 has been implicated in the progression of several cancers by virtue of its influence on progression of the G1/S phase of the cell cycle. However, little is known about the possible roles of cyclin D2 and D3 in colorectal cancers (CRCs).
  
  
  METHODS
  We investigated the expression levels of cyclin D2 and D3 in 84 CRC specimens. Antigen expression was determined by immunohistochemical analysis of cyclin D1, D2, D3, p16INK4A and Ki67 on tissue microarrays constructed using core samples from tumour centres and margins.
  
  
  RESULTS
  For the whole cohort, expression of cyclin D2 at the margin was associated with vascular invasion (P = 0.039), lymph node metastasis (P = 0.020) and liver metastasis (P < 0.001). In patients with stage I and II tumours (n = 84), elevated cyclin D2 and D3 were associated with vascular invasion (P = 0.014 and 0.028 respectively), liver metastasis (P = 0.001 and 0.007 respectively) and reduced disease specific survival (Cyclin D2, P < 0.022). No association was noted between the proliferative marker Ki-67 and the D-type cyclins.
  
  
  CONCLUSIONS
  These findings suggest that cyclin D2 expression at the invasive margin of CRCs is associated with liver metastasis and may serve as a useful prognostic marker and indicator of the need for adjuvant therapy.
authors.affiliation: Academic Unit of Surgery, Leeds Institute for Molecular Medicine, St James's University Hospital, Leeds, UK. sarkar_rupa@hotmail.com
authors.forename: R
authors.initials: R
authors.lastname: Sarkar
authors.forename: I A
authors.initials: IA
authors.lastname: Hunter
authors.forename: R
authors.initials: R
authors.lastname: Rajaganeshan
authors.forename: S L
authors.initials: SL
authors.lastname: Perry
authors.forename: P
authors.initials: P
authors.lastname: Guillou
authors.forename: D G
authors.initials: DG
authors.lastname: Jayne
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000368:Aged; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D056742:Cyclin D2 / Q000378:metabolism*; D056743:Cyclin D3 / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies
chemical_list: C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056742:Cyclin D2; D056743:Cyclin D3