mdm2-p53 interaction: Lack of correlation with the response to 5-fluorouracil in advanced colorectal cancer

Angelo Paradiso, G. Ranieri, G. Simone, N. Silvestris, A. Costa, M. De Lena, A. Leone, C. Vallejo, J. Lacava

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: We investigated the relevance of mdm2 and p53 primary tumour expression to the clinical outcome of a consecutive series of advanced colorectal cancer patients treated with a 5-fluorouracil-based chemotherapy. Methods: The expression of p53 and mdm2 was analyzed by an immunohistochemical assay in 80 formalin-fixed paraffin embedded primary tumour samples and related to the clinical response to 5-fluorouracil therapy and to the prognosis of the patients. In a subgroup of 46 tumours, the apoptotic index (AI) as determined by the Tunel technique was also assessed. Results: Nuclear immunostaining of p53 and mdm2 was present in 42 and 30% of the cases, respectively. No correlation was demonstrated between p53 and mdm2 expression (rs = -0.01; p>0.05). With regard to the clinical outcome, no statistical association was demonstrated among p53 and mdm2 expression, AI, probability of clinical response to treatment, time to progression, or overall survival. The subgroup of patients with a p53-negative/mdm2-positive tumour showed a worse response rate (15%); however, mdm2-positive/AI-negative tumours showed a 0% (0/7) probability of a clinical response as compared with 30% (9/30) of the remaining tumour patient subgroups; this also translated in a significantly worse overall survival probability (p = 0.01 by log rank). Conclusions: The analysis of mdm2 expression does not add significant clinical information in colorectal cancers with a different p53 status. Conversely, further analysis of AI seems to give data of a promising prognostic-predictive value.

Original languageEnglish
Pages (from-to)278-285
Number of pages8
JournalOncology
Volume62
Issue number3
DOIs
Publication statusPublished - 2002

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Fluorouracil
Colorectal Neoplasms
Neoplasms
Survival
Paraffin
Formaldehyde
Drug Therapy
Therapeutics

Keywords

  • 5-Fluorouracil
  • Advanced colorectal cancer
  • Apoptotic index
  • mdm2
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

mdm2-p53 interaction : Lack of correlation with the response to 5-fluorouracil in advanced colorectal cancer. / Paradiso, Angelo; Ranieri, G.; Simone, G.; Silvestris, N.; Costa, A.; De Lena, M.; Leone, A.; Vallejo, C.; Lacava, J.

In: Oncology, Vol. 62, No. 3, 2002, p. 278-285.

Research output: Contribution to journalArticle

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AU - Leone, A.

AU - Vallejo, C.

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N2 - Objective: We investigated the relevance of mdm2 and p53 primary tumour expression to the clinical outcome of a consecutive series of advanced colorectal cancer patients treated with a 5-fluorouracil-based chemotherapy. Methods: The expression of p53 and mdm2 was analyzed by an immunohistochemical assay in 80 formalin-fixed paraffin embedded primary tumour samples and related to the clinical response to 5-fluorouracil therapy and to the prognosis of the patients. In a subgroup of 46 tumours, the apoptotic index (AI) as determined by the Tunel technique was also assessed. Results: Nuclear immunostaining of p53 and mdm2 was present in 42 and 30% of the cases, respectively. No correlation was demonstrated between p53 and mdm2 expression (rs = -0.01; p>0.05). With regard to the clinical outcome, no statistical association was demonstrated among p53 and mdm2 expression, AI, probability of clinical response to treatment, time to progression, or overall survival. The subgroup of patients with a p53-negative/mdm2-positive tumour showed a worse response rate (15%); however, mdm2-positive/AI-negative tumours showed a 0% (0/7) probability of a clinical response as compared with 30% (9/30) of the remaining tumour patient subgroups; this also translated in a significantly worse overall survival probability (p = 0.01 by log rank). Conclusions: The analysis of mdm2 expression does not add significant clinical information in colorectal cancers with a different p53 status. Conversely, further analysis of AI seems to give data of a promising prognostic-predictive value.

AB - Objective: We investigated the relevance of mdm2 and p53 primary tumour expression to the clinical outcome of a consecutive series of advanced colorectal cancer patients treated with a 5-fluorouracil-based chemotherapy. Methods: The expression of p53 and mdm2 was analyzed by an immunohistochemical assay in 80 formalin-fixed paraffin embedded primary tumour samples and related to the clinical response to 5-fluorouracil therapy and to the prognosis of the patients. In a subgroup of 46 tumours, the apoptotic index (AI) as determined by the Tunel technique was also assessed. Results: Nuclear immunostaining of p53 and mdm2 was present in 42 and 30% of the cases, respectively. No correlation was demonstrated between p53 and mdm2 expression (rs = -0.01; p>0.05). With regard to the clinical outcome, no statistical association was demonstrated among p53 and mdm2 expression, AI, probability of clinical response to treatment, time to progression, or overall survival. The subgroup of patients with a p53-negative/mdm2-positive tumour showed a worse response rate (15%); however, mdm2-positive/AI-negative tumours showed a 0% (0/7) probability of a clinical response as compared with 30% (9/30) of the remaining tumour patient subgroups; this also translated in a significantly worse overall survival probability (p = 0.01 by log rank). Conclusions: The analysis of mdm2 expression does not add significant clinical information in colorectal cancers with a different p53 status. Conversely, further analysis of AI seems to give data of a promising prognostic-predictive value.

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