Expression of the thymidine phosphorylase gene in epithelial ovarian cancer.
Thymidine phosphorylase (TP) is associated with angiogenesis and the progression of solid tumours. High intracellular levels of this enzyme indicate increased chemosensitivity to pyrimidine antimetabolites. TP gene expression in 56 cases of epithelial ovarian cancer (27 of serous, 10 mucinous, 12 endometrioid, five clear cell and two undifferentiated) were analysed by polymerase chain reaction of RNA after reverse transcription. These included eight of low malignant potential. Twenty were stage I, four stage II, 27 stage III and five stage IV. The level of TP gene expression was presented by the relative yield of the TP gene to the beta2-microglobulin gene. TP gene expression ranged from 0.19 to 5.38 (median 0.93). The value of TP gene expression in stage III-IV was significantly higher than that of TP gene expression in stage I-II (P = 0.0005). Histological grade significantly associated with TP gene expression (P = 0.008), but histological subtype did not (P = 0.166). A follow-up study of 34 cases after complete resection of the primary tumours by surgical operation was performed. TP gene expression of the cases with recurrence showed significantly higher levels compared to cases without recurrence (P = 0.049). Survival data were available for 47 of the 56 patients. The prognosis of the patients with high TP gene expression (equal to, or greater than, median) was to be significantly worse than patients with low TP gene expression (less than median) (P = 0.021). The TP gene expression level may play one of the key roles in the biology of ovarian epithelial cancer and define a more aggressive tumour phenotype. A new therapeutic intervention mediated by TP protein activity is anticipated.
Hata
K
K
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan.
Kamikawa
T
T
Arao
S
S
Tashiro
H
H
Katabuchi
H
H
Okamura
H
H
Fujiwaki
R
R
Miyazaki
K
K
Fukumoto
M
M
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013939:Thymidine Phosphorylase / Q000235:genetics*
D013939:Thymidine Phosphorylase