title: Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients.
abstract: 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.
authors.affiliation: Clinical Experimental Oncology Laboratory, Oncology Institute, Bari, Italy. anpara@tin.it
authors.forename: A
authors.initials: A
authors.lastname: Paradiso
authors.forename: G
authors.initials: G
authors.lastname: Simone
authors.forename: S
authors.initials: S
authors.lastname: Petroni
authors.forename: B
authors.initials: B
authors.lastname: Leone
authors.forename: C
authors.initials: C
authors.lastname: Vallejo
authors.forename: J
authors.initials: J
authors.lastname: Lacava
authors.forename: A
authors.initials: A
authors.lastname: Romero
authors.forename: M
authors.initials: M
authors.lastname: Machiavelli
authors.forename: M
authors.initials: M
authors.lastname: De Lena
authors.forename: C J
authors.initials: CJ
authors.lastname: Allegra
authors.forename: P G
authors.initials: PG
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D013940:Thymidylate Synthase