Thymidylate synthase expression in epithelial ovarian cancer: relationship with thymidine phosphorylase expression and prognosis.
OBJECTIVE
Thymidylate synthase (TS) and thymidine phosphorylase (TP) are important enzymes involved in the de novo DNA synthesis and the salvage pathways for pyrimidine, respectively. Our purpose was to determine whether the gene expression of TS together with TP correlate with prognosis in epithelial ovarian cancer.


METHODS
TS gene expression was analyzed by reverse transcription-polymerase chain reaction in 20 samples from normal ovaries and 56 epithelial ovarian cancers previously studied regarding TP gene expression. TS and TP protein localization was examined by immunohistochemistry.


RESULTS
TS gene expression was significantly higher in epithelial ovarian cancer than in normal ovaries (p = 0.001). In patients with epithelial ovarian cancer, TS gene expression did not correlate with patient age, clinical stage, histologic type, or histologic grade. High TS gene expression (> median) significantly correlated with a poorer survival (p = 0.02). No significant correlation between TS and TP gene expression and different immunoreactivity patterns were found. Combined analysis of TS and TP gene expression demonstrated that the relative risk of death for tumors with high TS and high TP expression was greater than that for either only high TS or high TP gene expression (p = 0.002).


CONCLUSIONS
TS and TP combined may indicate a poor prognosis for patients with epithelial ovarian cancer.
Fujiwaki
R
R
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan.
Hata
K
K
Nakayama
K
K
Fukumoto
M
M
Miyazaki
K
K
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D010053:Ovary / Q000201:enzymology / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000096:biosynthesis* / Q000235:genetics; D013940:Thymidylate Synthase / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase