Thymidylate synthase expression in resectable and unresectable pancreatic cancer: role as predictive or prognostic marker?
OBJECTIVE
Thymidylate synthase (TS) is an important enzyme for DNA synthesis and the target for 5-fluorouracil (5-FU). Its expression may determine the outcome of patients with gastrointestinal cancers. We examined the prognostic and predictive value of TS-protein expression in patients with ductal adenocarcinoma of the pancreas.


METHODS
TS expression from 131 patients with ductal adenocarcinoma of the pancreas was analyzed by immunohistochemistry in paraffin-embedded primary tumour specimens or biopsies.


RESULTS
The median disease-specific survival among all patients (n=131) was 13 months. The invasion depth, the presence of metastases, grading and Union Internationale Contre le Cancer [International Union Against Cancer] (UICC) stage were associated with survival. Among resected patients (n=98), a difference in median survival was seen in the group receiving postoperative adjuvant treatment (21.1 months) compared with the group treated by surgery alone (12.4 months) (p=0.025). Low- and high-TS immunoreactivity was present in 74 (56%) and 56 (43%) of the cancers, respectively. One sample was not evaluable. No difference in median survival was observed among low- and high-TS-expressing tumours. Among patients undergoing resection and receiving postoperative intra-arterial chemotherapy (n=23), a marked trend to a longer median survival was seen for the group with low-TS-expressing tumours compared with the corresponding high-TS group (25.0 vs 16.0 months) (p=0.3834). There was no difference in survival among all palliative treated patients with low- and high-TS-expressing tumours.


CONCLUSIONS
Especially patients undergoing tumour resection with low-TS values seemed to have taken advantage from an intensified postoperative chemotherapeutic protocol. However due to the heterogeneous group of patients in the present report, larger trials of more homogenous patient populations will be necessary to confirm this hypothesis.
Formentini
Andrea
A
Department of Visceral and Transplantation Surgery, University of Ulm, Steinhoevelstrasse 9, 89075, Ulm, Germany.
Sander
Sylvia
S
Denzer
Stephanie
S
Straeter
Joern
J
Henne-Bruns
Doris
D
Kornmann
Marko
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends; D013940:Thymidylate Synthase / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase