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.

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Keywords Immunohistochemistry, Pancreatic head cancer, Periampullary cancer, Prognosis, Thymidylate synthase
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Journal European Journal of Surgical Oncology
van der Zee, J, van Eijck, C.H.J, Hop, W.C.J, van Dekken, H, Dicheva, B.M, Seynhaeve, A.L.B, … ten Hagen, T.L.M. (2012). Expression and prognostic significance of thymidylate synthase (TS) in pancreatic head and periampullary cancer. European Journal of Surgical Oncology, 38(11), 1058–1064. doi:10.1016/j.ejso.2012.04.013