A new prognostic factor for colorectal carcinoma, thymidylate synthase, and its therapeutic significance.
BACKGROUND
Expression of thymidylate synthase (TS) has been studied as a mechanism of drug resistance and a prognostic factor for various cancers.


METHODS
The relation between TS expression in surgically resected specimens and patient survival was examined in 86 patients with colorectal carcinoma (58 of whom received adjuvant chemotherapy and 28 who did not) who had been followed for 10 years. Immunohistochemical demonstration of the protein was achieved using an anti-TS polyclonal antibody.


RESULTS
In the 58 patients who received chemotherapy, the overall 10-year survival rate was 77.8% for patients with TS positive tumors and 89.4% for patients with TS negative tumors (difference not significant). However, in the 28 patients who did not receive chemotherapy, these figures were only 42.9% and 85.7%, respectively (P < 0.05). Multivariate analysis also revealed TS expression to be a significant variable for predicting postoperative survival (P < 0.05).


CONCLUSIONS
TS expression can be used as an independent prognostic factor for patients with colorectal carcinoma. Patients with TS positive tumors have a poorer prognosis than those with TS negative lesions and therefore should receive special consideration with regard to chemotherapy.
Yamachika
T
T
Laboratory of Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Nakanishi
H
H
Inada
K
K
Tsukamoto
T
T
Kato
T
T
Fukushima
M
M
Inoue
M
M
Tatematsu
M
M
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000906:Antibodies; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D004396:Coloring Agents; D003594:Cytoplasmic Granules / Q000201:enzymology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000627:therapeutic use; D015999:Multivariate Analysis; D011379:Prognosis; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000032:analysis* / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D000906:Antibodies; D014408:Biomarkers, Tumor; D004396:Coloring Agents; D016685:Mitomycin; D013940:Thymidylate Synthase