Analysis of key cell-cycle checkpoint proteins in colorectal tumours

J. A. McKay, J. J. Douglas, V. G. Ross, Stephanie Curran, Joseph Loane, Fazle Ahmed, J. Cassidy, H. L. McLeod, Graeme Ian Murray

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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)l 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 greater than or equal to 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 ell-cycle checkpoints is a common occurrence in colorectal tumours and may be an important 1 therapeutic target. Copyright (C) 2002 John Wiley Sons, Ltd.

Original languageEnglish
Pages (from-to)386-393
Number of pages7
JournalThe Journal of pathology
Volume196
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • cell cycle
  • checkpoints
  • colorectal cancer
  • prognosis
  • immunohistochemistry
  • DEPENDENT KINASE INHIBITOR
  • PROGNOSTIC-SIGNIFICANCE
  • NUCLEAR ANTIGEN
  • POOR-PROGNOSIS
  • RETINOBLASTOMA PROTEIN
  • GENETIC ALTERATIONS
  • CANCER
  • EXPRESSION
  • P53
  • CARCINOMA

Cite this

McKay, J. A., Douglas, J. J., Ross, V. G., Curran, S., Loane, J., Ahmed, F., Cassidy, J., McLeod, H. L., & Murray, G. I. (2002). Analysis of key cell-cycle checkpoint proteins in colorectal tumours. The Journal of pathology, 196(4), 386-393. https://doi.org/10.1002/path.1053