Topoisomerase‐I, thymidylate synthase primary tumour expression and clinical efficacy of 5‐FU/CPT‐11 chemotherapy in advanced colorectal cancer patients

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Abstract
While several studies have reported that thymidylate synthase (TS) tumour expression can be a reliable predictive marker of clinical response to 5‐Fluorouracil (5‐FU) for advanced colorectal cancer patients, only a few studies that searched for predictive factors of irinotecan (CPT‐11) clinical response are available. The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase‐I (Topo‐I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5‐FU/CPT‐11 chemotherapy. TS and Topo‐I immunostaining was observed in 76% and 43% of tumours, respectively, resulting in a significant relationship within each tumour (r=0.365, pvs. 28% of OR in low and high TS‐expressing tumours, respectively, p=ns); also, patients with different Topo‐I tumour expression did not show a different probability of OR (39% vs. 29% of OR in high and low Topo‐I expressing tumours, respectively; p=ns).The tumour expression of these 2 biomarkers also did not impact on time to progression and overall survival of patients. Furthermore, the combined analysis of TS and Topo‐I tumour status did not permit to individualize subgroups of patients with different probability of OR. With multivariate analysis, only patient Performance Status significantly impacted on OS (Hazard ratio 4.87; p=0.02) of these patients. We can conclude that high TS tumour expression seems not to preclude a clinical activity for 5‐FU/CPT‐11 polichemotherapy in advanced colorectal cancer patients; furthermore, clinical response and prognosis of colorectal cancer patients treated with 5‐FU/CPT‐11 regimen do not differ in tumours with different TS or Topo‐I expression.