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

Research output: Contribution to journalArticle

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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., ... 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

Analysis of key cell-cycle checkpoint proteins in colorectal tumours. / McKay, J. A.; Douglas, J. J.; Ross, V. G.; Curran, Stephanie; Loane, Joseph; Ahmed, Fazle; Cassidy, J.; McLeod, H. L.; Murray, Graeme Ian.

In: The Journal of pathology, Vol. 196, No. 4, 2002, p. 386-393.

Research output: Contribution to journalArticle

McKay, JA, Douglas, JJ, Ross, VG, Curran, S, Loane, J, Ahmed, F, Cassidy, J, McLeod, HL & Murray, GI 2002, 'Analysis of key cell-cycle checkpoint proteins in colorectal tumours', The Journal of pathology, vol. 196, no. 4, pp. 386-393. https://doi.org/10.1002/path.1053
McKay JA, Douglas JJ, Ross VG, Curran S, Loane J, Ahmed F et al. Analysis of key cell-cycle checkpoint proteins in colorectal tumours. The Journal of pathology. 2002;196(4):386-393. https://doi.org/10.1002/path.1053
McKay, J. A. ; Douglas, J. J. ; Ross, V. G. ; Curran, Stephanie ; Loane, Joseph ; Ahmed, Fazle ; Cassidy, J. ; McLeod, H. L. ; Murray, Graeme Ian. / Analysis of key cell-cycle checkpoint proteins in colorectal tumours. In: The Journal of pathology. 2002 ; Vol. 196, No. 4. pp. 386-393.
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T1 - Analysis of key cell-cycle checkpoint proteins in colorectal tumours

AU - McKay, J. A.

AU - Douglas, J. J.

AU - Ross, V. G.

AU - Curran, Stephanie

AU - Loane, Joseph

AU - Ahmed, Fazle

AU - Cassidy, J.

AU - McLeod, H. L.

AU - Murray, Graeme Ian

PY - 2002

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N2 - 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.

AB - 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.

KW - cell cycle

KW - checkpoints

KW - colorectal cancer

KW - prognosis

KW - immunohistochemistry

KW - DEPENDENT KINASE INHIBITOR

KW - PROGNOSTIC-SIGNIFICANCE

KW - NUCLEAR ANTIGEN

KW - POOR-PROGNOSIS

KW - RETINOBLASTOMA PROTEIN

KW - GENETIC ALTERATIONS

KW - CANCER

KW - EXPRESSION

KW - P53

KW - CARCINOMA

U2 - 10.1002/path.1053

DO - 10.1002/path.1053

M3 - Article

VL - 196

SP - 386

EP - 393

JO - The Journal of pathology

JF - The Journal of pathology

SN - 0022-3417

IS - 4

ER -