Rb, mc1-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer

H. H J Backus, J. M G H Van Riel, C. J. Van Groeningen, W. Vos, D. F. Dukers, E. Bloemena, D. Wouters, H. M. Pinedo, G. J. Peters

Research output: Contribution to journalArticle

Abstract

Background: Thymidylate synthase (TS) has been associated with clinical outcome in disseminated colorectal cancer. However, many patients with low TS expression still fail to respond to treatment. Therefore, we studied the cell cycle proteins, Rb, E2F2, Ki67, p21 and p53 and the apoptotic proteins, mcl-1, bax, bcl-xl, bcl-2, Fas receptor, Fas ligand, caspase-3, M30 and PARP as potential predictive factors. Patients and methods: In biopsy specimens of liver metastases from 31 colorectal cancer patients, protein expression was retrospectively determined by immunohistochemistry and related to response to hepatic arterial or intravenous (i.v.) 5-fluorouracil (5-FU) treatment, time to tumour progression (TTP) and overall survival. Results: Expression of both p53 and Rb correlated with survival benefit after 5-FU treatment. A median survival time of 79 weeks was found in patients with high levels of p53 or Rb compared to 36 and 44 weeks for patients expressing low levels of p53 (P = 0.027) or Rb (P = 0.030), respectively. Multivariate analysis showed that p53 was the best predictor of survival independent of sex, age or prior treatment. Following 5-FU hepatic arterial infusion, patients with a high TS expression had a shorter survival time than those with a low expression (P = 0.025). The anti-apoptotic protein mcl-1 was the only factor, which correlated with response to 5-FU treatment. Thirty-five percent of patients with a diffuse mcl-1 expression responded whereas ninety percent of patients with a peri-nuclear expression responded (P = 0.041). Conclusions: These results indicate that besides TS, also Rb, p53 and mcl-1 are correlated with clinical outcome in patients with liver metastases from colorectal cancer.

Original languageEnglish (US)
Pages (from-to)779-785
Number of pages7
JournalAnnals of Oncology
Volume12
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Colorectal Neoplasms
Neoplasm Metastasis
Liver
Thymidylate Synthase
Fluorouracil
Survival
CD95 Antigens
Therapeutics
Cell Cycle Proteins
Apoptosis Regulatory Proteins
Fas Ligand Protein
Caspase 3
Proteins
Multivariate Analysis
Immunohistochemistry
Biopsy
Neoplasms

Keywords

  • 5-FU
  • Colorectal cancer
  • mcl-1
  • p53 and thymidylate synthase
  • Rb

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Backus, H. H. J., Van Riel, J. M. G. H., Van Groeningen, C. J., Vos, W., Dukers, D. F., Bloemena, E., ... Peters, G. J. (2001). Rb, mc1-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer. Annals of Oncology, 12(6), 779-785. https://doi.org/10.1023/A:1011112227044

Rb, mc1-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer. / Backus, H. H J; Van Riel, J. M G H; Van Groeningen, C. J.; Vos, W.; Dukers, D. F.; Bloemena, E.; Wouters, D.; Pinedo, H. M.; Peters, G. J.

In: Annals of Oncology, Vol. 12, No. 6, 2001, p. 779-785.

Research output: Contribution to journalArticle

Backus, HHJ, Van Riel, JMGH, Van Groeningen, CJ, Vos, W, Dukers, DF, Bloemena, E, Wouters, D, Pinedo, HM & Peters, GJ 2001, 'Rb, mc1-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer', Annals of Oncology, vol. 12, no. 6, pp. 779-785. https://doi.org/10.1023/A:1011112227044
Backus, H. H J ; Van Riel, J. M G H ; Van Groeningen, C. J. ; Vos, W. ; Dukers, D. F. ; Bloemena, E. ; Wouters, D. ; Pinedo, H. M. ; Peters, G. J. / Rb, mc1-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer. In: Annals of Oncology. 2001 ; Vol. 12, No. 6. pp. 779-785.
@article{b76690d666c84682b05e713c45bcab26,
title = "Rb, mc1-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer",
abstract = "Background: Thymidylate synthase (TS) has been associated with clinical outcome in disseminated colorectal cancer. However, many patients with low TS expression still fail to respond to treatment. Therefore, we studied the cell cycle proteins, Rb, E2F2, Ki67, p21 and p53 and the apoptotic proteins, mcl-1, bax, bcl-xl, bcl-2, Fas receptor, Fas ligand, caspase-3, M30 and PARP as potential predictive factors. Patients and methods: In biopsy specimens of liver metastases from 31 colorectal cancer patients, protein expression was retrospectively determined by immunohistochemistry and related to response to hepatic arterial or intravenous (i.v.) 5-fluorouracil (5-FU) treatment, time to tumour progression (TTP) and overall survival. Results: Expression of both p53 and Rb correlated with survival benefit after 5-FU treatment. A median survival time of 79 weeks was found in patients with high levels of p53 or Rb compared to 36 and 44 weeks for patients expressing low levels of p53 (P = 0.027) or Rb (P = 0.030), respectively. Multivariate analysis showed that p53 was the best predictor of survival independent of sex, age or prior treatment. Following 5-FU hepatic arterial infusion, patients with a high TS expression had a shorter survival time than those with a low expression (P = 0.025). The anti-apoptotic protein mcl-1 was the only factor, which correlated with response to 5-FU treatment. Thirty-five percent of patients with a diffuse mcl-1 expression responded whereas ninety percent of patients with a peri-nuclear expression responded (P = 0.041). Conclusions: These results indicate that besides TS, also Rb, p53 and mcl-1 are correlated with clinical outcome in patients with liver metastases from colorectal cancer.",
keywords = "5-FU, Colorectal cancer, mcl-1, p53 and thymidylate synthase, Rb",
author = "Backus, {H. H J} and {Van Riel}, {J. M G H} and {Van Groeningen}, {C. J.} and W. Vos and Dukers, {D. F.} and E. Bloemena and D. Wouters and Pinedo, {H. M.} and Peters, {G. J.}",
year = "2001",
doi = "10.1023/A:1011112227044",
language = "English (US)",
volume = "12",
pages = "779--785",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Rb, mc1-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer

AU - Backus, H. H J

AU - Van Riel, J. M G H

AU - Van Groeningen, C. J.

AU - Vos, W.

AU - Dukers, D. F.

AU - Bloemena, E.

AU - Wouters, D.

AU - Pinedo, H. M.

AU - Peters, G. J.

PY - 2001

Y1 - 2001

N2 - Background: Thymidylate synthase (TS) has been associated with clinical outcome in disseminated colorectal cancer. However, many patients with low TS expression still fail to respond to treatment. Therefore, we studied the cell cycle proteins, Rb, E2F2, Ki67, p21 and p53 and the apoptotic proteins, mcl-1, bax, bcl-xl, bcl-2, Fas receptor, Fas ligand, caspase-3, M30 and PARP as potential predictive factors. Patients and methods: In biopsy specimens of liver metastases from 31 colorectal cancer patients, protein expression was retrospectively determined by immunohistochemistry and related to response to hepatic arterial or intravenous (i.v.) 5-fluorouracil (5-FU) treatment, time to tumour progression (TTP) and overall survival. Results: Expression of both p53 and Rb correlated with survival benefit after 5-FU treatment. A median survival time of 79 weeks was found in patients with high levels of p53 or Rb compared to 36 and 44 weeks for patients expressing low levels of p53 (P = 0.027) or Rb (P = 0.030), respectively. Multivariate analysis showed that p53 was the best predictor of survival independent of sex, age or prior treatment. Following 5-FU hepatic arterial infusion, patients with a high TS expression had a shorter survival time than those with a low expression (P = 0.025). The anti-apoptotic protein mcl-1 was the only factor, which correlated with response to 5-FU treatment. Thirty-five percent of patients with a diffuse mcl-1 expression responded whereas ninety percent of patients with a peri-nuclear expression responded (P = 0.041). Conclusions: These results indicate that besides TS, also Rb, p53 and mcl-1 are correlated with clinical outcome in patients with liver metastases from colorectal cancer.

AB - Background: Thymidylate synthase (TS) has been associated with clinical outcome in disseminated colorectal cancer. However, many patients with low TS expression still fail to respond to treatment. Therefore, we studied the cell cycle proteins, Rb, E2F2, Ki67, p21 and p53 and the apoptotic proteins, mcl-1, bax, bcl-xl, bcl-2, Fas receptor, Fas ligand, caspase-3, M30 and PARP as potential predictive factors. Patients and methods: In biopsy specimens of liver metastases from 31 colorectal cancer patients, protein expression was retrospectively determined by immunohistochemistry and related to response to hepatic arterial or intravenous (i.v.) 5-fluorouracil (5-FU) treatment, time to tumour progression (TTP) and overall survival. Results: Expression of both p53 and Rb correlated with survival benefit after 5-FU treatment. A median survival time of 79 weeks was found in patients with high levels of p53 or Rb compared to 36 and 44 weeks for patients expressing low levels of p53 (P = 0.027) or Rb (P = 0.030), respectively. Multivariate analysis showed that p53 was the best predictor of survival independent of sex, age or prior treatment. Following 5-FU hepatic arterial infusion, patients with a high TS expression had a shorter survival time than those with a low expression (P = 0.025). The anti-apoptotic protein mcl-1 was the only factor, which correlated with response to 5-FU treatment. Thirty-five percent of patients with a diffuse mcl-1 expression responded whereas ninety percent of patients with a peri-nuclear expression responded (P = 0.041). Conclusions: These results indicate that besides TS, also Rb, p53 and mcl-1 are correlated with clinical outcome in patients with liver metastases from colorectal cancer.

KW - 5-FU

KW - Colorectal cancer

KW - mcl-1

KW - p53 and thymidylate synthase

KW - Rb

UR - http://www.scopus.com/inward/record.url?scp=0034743398&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034743398&partnerID=8YFLogxK

U2 - 10.1023/A:1011112227044

DO - 10.1023/A:1011112227044

M3 - Article

C2 - 11484952

AN - SCOPUS:0034743398

VL - 12

SP - 779

EP - 785

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 6

ER -