Analysis of key cell-cycle checkpoint proteins in colorectal tumours

Judith A McKay, Joy J Douglas, Val G Ross, Stephanie Curran, Joseph F Loane, Fareeda Y Ahmed, Jim Cassidy, Howard L McLeod, Graeme I Murray

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)386-93
Number of pages8
JournalThe Journal of Pathology
Volume196
Issue number4
DOIs
Publication statusPublished - Apr 2002

Keywords

  • Adenocarcinoma
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Cycle Proteins
  • Colorectal Neoplasms
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Proteins
  • Prognosis
  • Survival Rate
  • Tumor Markers, Biological

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