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


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).


CONCLUSIONS
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.
Laboratory of Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. j.a.vanderzee@erasmusmc.nl
J A
JA
van der Zee
C H J
CH
van Eijck
W C J
WC
Hop
H
H
van Dekken
B M
BM
Dicheva
A L B
AL
Seynhaeve
G A
GA
Koning
A M M
AM
Eggermont
T L M
TL
Ten Hagen
D000230:Adenocarcinoma / Q000201:enzymology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D059248:Chemoradiotherapy; D003138:Common Bile Duct Neoplasms / Q000201:enzymology* / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000628:therapy; D011379:Prognosis; D013940:Thymidylate Synthase / Q000032:analysis*
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D005472:Fluorouracil