Analysis of key cell‐cycle checkpoint proteins in colorectal tumours

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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 ⩾2 cell‐cycle control factors. Expression of cyclin D1 protein was correlated with both p21 (pp=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 pp=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 itwas 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. Copyright © 2002 John Wiley & Sons, Ltd.
Funding Information
  • University of Aberdeen Development TRUST