Influence of thymidylate synthase and p53 protein expression on clinical outcome in patients with colorectal cancer.
OBJECTIVE
Thymidylate synthase (TS) and tumor suppressor p53 are two proteins with an influence on tumor resistance to radio-chemotherapy that is well known. For this reason we tested the effect of TS and p53 expression on clinical outcome (tumor recurrence and survival) in patients after curative tumor resection, especially in patients who received adjuvant radio-chemotherapy.


METHODS
A total of 120 patients with colorectal cancer were included in the study. A curative resection was possible in 83 patients, and 30 of this group received adjuvant therapy. For the immunohistochemical staining of tumor specimens, monoclonal antibody (mAb) TS 106 against TS and mAb DO-1 against p53 protein were used. TS positivity was defined as a moderate to high staining intensity in the cytoplasma of cells and p53 positivity as nuclear staining of tumor cells in >10% of these cells.


RESULTS
Thymidylate synthase immunoreactivity was found in 59% of all cases and p53 staining in 51%. No relation between clinicopathological features and p53 expression was found in contrast to TS expression, where a highly significant association of TS-positive cases with tumor invasion (pT) was observed. Curatively resected patients with a TS-positive tumor developed tumor recurrence/distant metastases significantly more often than TS negative tumors. The same result was found when comparing p53-positive with p53-negative tumors and TS+/p53+ with TS-/p53- tumors. TS expression was highly significantly associated with poor survival and was the strongest independent prognostic factor in multivariate analysis, followed by lymph node status.


CONCLUSIONS
Thymidylate synthase expression seems to be an independent prognostic factor and a possible predictor of tumor recurrence in patients with colorectal cancer.
Surgical Research Laboratory, University Clinic of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. broll@uni-luebeck.de
R
R
Broll
P
P
Busch
M
M
Duchrow
E
E
Oevermann
O
O
Schwandner
S
S
Farke
H P
HP
Bruch
U
U
Windhövel
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D001706:Biopsy / Q000379:methods; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000517:prevention & control; D011379:Prognosis; D011446:Prospective Studies; D013940:Thymidylate Synthase / Q000096:biosynthesis* / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D013940:Thymidylate Synthase