title: Expression of cyclin D1a and D1b as predictive factors for treatment response in colorectal cancer.
abstract: BACKGROUND
  The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC).
  
  
  METHODS
  Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses.
  
  
  RESULTS
  Neither cyclin D1a nor D1b showed any prognostic value in CRC or colon cancer patients. However, high cyclin D1a predicted benefit from adjuvant therapy measured in 5-year relapse-free survival (RFS) and CRC-specific survival (CSS) compared to surgery alone in colon cancer (P=0.012 and P=0.038, respectively) and especially in colon cancer stage III patients (P=0.005 and P=0.019, respectively) in univariate analyses. An interaction between treatment group and cyclin D1a could be shown for RFS (P=0.004) and CSS (P=0.025) in multivariate analysis.
  
  
  CONCLUSIONS
  Our study identifies high cyclin D1a protein expression as a positive predictive factor for the benefit of adjuvant 5-FU/LEV treatment in colon cancer, particularly in stage III colon cancer.
authors.affiliation: Institute of Medicine, Section of Oncology, University of Bergen, Bergen 5021, Norway.
authors.forename: M P
authors.initials: MP
authors.lastname: Myklebust
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: T H
authors.initials: TH
authors.lastname: Tran
authors.forename: H
authors.initials: H
authors.lastname: Rui
authors.forename: E S
authors.initials: ES
authors.lastname: Knudsen
authors.forename: H
authors.initials: H
authors.lastname: Elsaleh
authors.forename: Ø
authors.initials: Ø
authors.lastname: Fluge
authors.forename: B
authors.initials: B
authors.lastname: Vonen
authors.forename: H E
authors.initials: HE
authors.lastname: Myrvold
authors.forename: S
authors.initials: S
authors.lastname: Leh
authors.forename: K M
authors.initials: KM
authors.lastname: Tveit
authors.forename: R G
authors.initials: RG
authors.lastname: Pestell
authors.forename: O
authors.initials: O
authors.lastname: Dahl
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy / Q000379:methods; D019938:Cyclin D1 / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007978:Levamisole / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1; D007978:Levamisole; D005472:Fluorouracil