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

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.

Deciphering the potential value of 5-fluorouracil metabolic enzymes in predicting prognosis and treatment response of colorectal cancer patients

“…In contrast, CRC patients having high levels of TS had poorer survival compared to those with low TS levels (19, 20). Similarly, patients with TS negative tumors had a better outcome than those with TS positive tumors in gastric and gastro-esophageal adenocarcinoma (21). Gao et al (22) also showed a correlation of high TS expression with unfavorable survival and lower response rates to FU-based chemotherapy in gastric cancer.…”

Role of pH in Regulating Cancer Pyrimidine Synthesis

“…The optimal pH range in leukemia is 7.0-8.1 [147]. TS is also a prognostic biomarker in tumors and is associated with drug resistanc [148][149][150][151][152][153].…”

“…TS is also a prognostic biomarker in tumors and is associated with drug resistance [ 148 , 149 , 150 , 151 , 152 , 153 ].…”