title: Analysis of key cell-cycle checkpoint proteins in colorectal tumours.
abstract: Aberrations in the components of cell-cycle checkpoints are a common feature of many tumours and several have been shown to have prognostic significance in colorectal cancer. In this study, seven components of cell-cycle control [cyclin D1, retinoblastoma (pRb), p21, p27, p16, p53, and proliferating cell nuclear antigen (PCNA)] were examined in a large series of well-characterized colorectal adenocarcinomas using immunohistochemistry to ascertain co-regulation and influence on survival. The majority (92%) of the tumours had abnormal staining of > or =2 cell-cycle control factors. Expression of cyclin D1 protein was correlated with both p21 (p<0.001) and p27 (p=0.033), suggesting co-regulation of these proteins in colorectal tumours. Only cyclin D1 (p=0.048) and p53 (p=0.025) were directly associated with PCNA levels, suggesting a more important role in the proliferative capacity of tumour cells. Significant associations between cell cycle-related proteins and clinicopathological data were observed: cyclin D1 and p53 proteins were correlated with patient age (p=0.042 and p<0.001, respectively) and p53 (p=0.01) and p21 (p=0.024) proteins were associated with tumour site. Expression of cyclin D1 protein was the only protein examined that was related to improved outcome in these patients (p=0.0266), but it was not an independent predictor of survival. These results suggest that loss of control of cell-cycle checkpoints is a common occurrence in colorectal tumours and may be an important therapeutic target.
authors.affiliation: Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
authors.forename: Judith A
authors.initials: JA
authors.lastname: McKay
authors.forename: Joy J
authors.initials: JJ
authors.lastname: Douglas
authors.forename: Val G
authors.initials: VG
authors.lastname: Ross
authors.forename: Stephanie
authors.initials: S
authors.lastname: Curran
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Loane
authors.forename: Fareeda Y
authors.initials: FY
authors.lastname: Ahmed
authors.forename: Jim
authors.initials: J
authors.lastname: Cassidy
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Murray
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins