Expression and prognostic significance of thymidylate synthase (TS) in pancreatic head and periampullary cancer

Eur J Surg Oncol. 2012 Nov;38(11):1058-64. doi: 10.1016/j.ejso.2012.04.013. Epub 2012 May 24.

Abstract

Background: Pancreatic cancer has a dismal prognosis. Attempts have been made to improve outcome by several 5-FU based adjuvant treatment regimens. However, the results are conflicting. There seems to be a continental divide with respect to the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been presented showing a different response of pancreatic head and periampullary cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been associated with improved outcome following 5-FU based adjuvant treatment in gastrointestinal cancer. This prompted us to determine the differential expression and prognostic value of TS in pancreatic head and periampullary cancer.

Patients and methods: TS protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 212 patients following microscopic radical resection (R0) of pancreatic head (n = 98) or periampullary cancer (n = 114). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and conventional prognostic factors.

Results: High cytosolic TS expression was present in 26% of pancreatic head tumours and 37% of periampullary tumours (p = .11). Furthermore, TS was an independent factor predicting favourable outcome following curative resection of pancreatic head cancer (p = .003, .001 and .001 for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was not associated with outcome (all p > .10).

Conclusion: TS, was found to be poorly expressed in both pancreatic head and periampullary cancer and identified as an independent prognostic factor following curative resection of pancreatic head cancer.

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Ampulla of Vater*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biomarkers, Tumor / analysis
  • Chemoradiotherapy
  • Common Bile Duct Neoplasms / enzymology*
  • Common Bile Duct Neoplasms / therapy
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / therapy
  • Prognosis
  • Thymidylate Synthase / analysis*

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Thymidylate Synthase
  • Fluorouracil