Thymidylate synthase expression and prognosis of patients with gastrointestinal cancers receiving adjuvant chemotherapy: a review.
OBJECTIVE
Many studies have been published that report an association between thymidylate synthase (TS) and response to fluoropyrimidine-based chemotherapy and the overall outcome of patients with gastrointestinal cancer. The results have given rise to the possibility that, by determination of TS levels, the physician may decide if the patient has a potential benefit from fluoropyrimidine-based treatment, similar to measurements of oestrogen receptors in breast cancer. The purpose of this review is to summarize critically the reports on TS measurement in gastrointestinal cancer, focusing on the adjuvant fluoropyrimidine treatment situation.


METHODS
We reviewed more than 20 studies that reported the association of TS with the clinical outcome in patients with gastrointestinal cancer who had undergone complete resection of the primary tumour only or were receiving additional adjuvant chemotherapy.


RESULTS
Patients with metastasized disease who expressed high TS levels display a low probability of responding to fluoropyrimidine-based treatment and have a poorer survival rate. Patients with high TS levels who undergo complete surgical resection of the primary tumour also have a poorer prognosis than those with tumours with low TS expression. In contrast to advanced disease and to surgery alone, patients with high TS levels appear to benefit, especially, from adjuvant fluoropyrimidine-based chemotherapy after complete primary tumour resection, while patients with low TS levels do not.


CONCLUSIONS
Patients with gastrointestinal cancers that express high TS levels have a poor prognosis with regard to fluoropyrimidine-based palliative chemotherapy or complete primary tumour resection. In contrast, patients with high TS levels might benefit from adjuvant fluoropyrimidine-based treatment after primary tumour resection. However, additional prospective studies are mandatory to define the precise role of TS in adjuvant therapy.
Formentini
Andrea
A
Department of Visceral and Transplantation Surgery, University of Ulm, Steinhoevelstrasse 9, 89075 Ulm, Germany.
Henne-Bruns
Doris
D
Kornmann
Marko
M
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D015201:Meta-Analysis as Topic; D009364:Neoplasm Recurrence, Local; D010166:Palliative Care; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis; D005641:Tegafur / Q000378:metabolism / Q000627:therapeutic use; D013940:Thymidylate Synthase / Q000032:analysis* / Q000235:genetics; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D005641:Tegafur; D013940:Thymidylate Synthase; D005472:Fluorouracil