A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma

Abstract EN

Aims and Background.

Patients in the United Kingdom with operable gastric and gastro-oesophageal junction (GOJ) tumours receive neoadjuvant chemotherapy.

Our aim was to study the expression of thymidylate synthase (TS) enzyme in pre-treatment diagnostic biopsy specimens and investigate its clinical usefulness.

Methods.

A single-centre study was carried out in 45 patients with gastric and GOJ adenocarcinoma treated with neo-adjuvant chemotherapy according to the MAGIC protocol.

TS expression was determined using immunohistochemistry.

>10% tumour nuclei expression of TS was used as cut-off for positivity.

Results.

Forty-one (91%) of the 45 tumours expressed TS.

There was no association between TS expression and lymph node status (P = 0.80), histological response (P = 0.30), and recurrence (P = 0.55).

On univariate analysis, only N-stage (P = 0.02) and vascular invasion (P = 0.04) were associated with a poor prognosis.

Patients with negative tumour TS expression had better outcome than those with positive expression.

The overall 5-year survival rate was 100% in the TS negative versus 56% in TS positive group, but the difference was not statistically significant (P = 0.17).

Conclusion.

TS expression should be studied in a larger series of gastro-oesophageal cancers as a potential prognostic marker of prognosis to neo-adjuvant chemotherapy.