Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients
| Autor: | Carlos Teodoro Vallejo, S. Petroni, P. G. Johnston, Bernardo Amadeo Leone, G.M. Simone, M. De Lena, J. A. Lacava, Carmen J. Allegra, M Machiavelli, A Romero, Angelo Paradiso |
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| Rok vydání: | 2000 |
| Předmět: |
p53
Adult Oncology Cancer Research medicine.medical_specialty Pathology Colorectal cancer medicine.medical_treatment Rectum colorectal cancer Antineoplastic Agents TS Thymidylate synthase predictive factor Internal medicine medicine Carcinoma Humans Neoplasm Metastasis Aged Chemotherapy biology business.industry Hazard ratio Regular Article Thymidylate Synthase Middle Aged Prognosis medicine.disease Immunohistochemistry Treatment Outcome medicine.anatomical_structure Fluorouracil biology.protein Methotrexate Tumor Suppressor Protein p53 Colorectal Neoplasms business medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1054/bjoc.1999.0964 |
| Popis: | The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated–5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53– cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively;P< 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P< 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34–1.01; two-sided P< 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85–1.26; two-sided P< 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy. © 2000 Cancer Research Campaign |
| Databáze: | OpenAIRE |
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