Topoisomerase I but not thymidylate synthase is associated with improved outcome in patients with resected colorectal cancer treated with irinotecan containing adjuvant chemotherapy.
BACKGROUND
Thymidylate synthase (TS) and Topoisomerase I (Topo I) are significant biomarkers in colorectal cancer (CRC). We aimed to study the expression of TS and Topo I in patients with resected CRC who received adjuvant chemotherapy and correlated it with clinical outcome.


METHODS
All patients diagnosed with CRC between 1989 and 2007 and treated with adjuvant chemotherapy within Hellenic Cooperative Oncology Group's (HeCOG) protocols, were identified. Archival paraffin-embedded tumor tissues were used for immunohistochemical detection of TS and Topo I. Immunohistochemistry was performed on tissue microarray slides using monoclonal antibodies against TS and Topo I. The results were correlated with survival (OS) and disease free survival (DFS).


RESULTS
A cohort of 498 patients with a median age of 61 years and Dukes' stage B (49%) and C (51%) fulfilled the criteria of the study. All patients received adjuvant 5-FU-based chemotherapy, 38% irinotecan-containing. Positive TS and Topo I expression was found in 43% and 48% of cases, respectively. Five-year OS was 74% and DFS was 68%. In univariate analysis no association of TS and Topo I expression with OS and DFS was identified. In multivariate analysis however, Topo I expression was associated with a reduced risk of death (HR = 0.61, 95% CI 0.42-0.88, p = 0.009). In the irinotecan-treated subgroup, those patients who expressed Topo I had a better OS (HR = 0.47, 95% CI 0.23-0.94, p = 0.033).


CONCLUSIONS
Patients with resected CRC expressing Topo I seem to benefit from irinotecan-containing adjuvant chemotherapy. However randomised prospective trials are needed to confirm these results.
Kostopoulos
Ioannis
I
Department of Medical Oncology "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Karavasilis
Vasilios
V
Karina
Maria
M
Bobos
Mattheos
M
Xiros
Nikolaos
N
Pentheroudakis
George
G
Kafiri
Georgia
G
Papakostas
Pavlos
P
Vrettou
Eleni
E
Fountzilas
George
G
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000601:surgery; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D000077146:Irinotecan; D013940:Thymidylate Synthase; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin