Expression of thymidine phosphorylase in epithelial ovarian cancer: correlation with angiogenesis, apoptosis, and ultrasound-derived peak systolic velocity.
OBJECTIVE
The objective of this study was to determine whether the expression of thymidine phosphorylase (TP) by epithelial ovarian cancer cells correlates with the density of microvessels within the tumor, apoptotic index (AI) within the tumor cells, and ultrasound-derived blood flow.


METHODS
Color Doppler imaging and pulsed Doppler spectral analysis ultrasonography were used to scan 44 patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of TP and the intratumoral density of microvessels by immunohistochemistry using antibodies to TP and factor-VIII-related antigen, respectively. Moreover, AI was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling methods.


RESULTS
Forty-four epithelial ovarian cancers were studied (6 low malignant potential, 15 serous cystadenocarcinoma, 9 mucinous cystadenocarcinoma, 8 endometrioid adenocarcinoma, 4 clear cell carcinoma, and 2 malignant Brenner tumors); 19 were Stage I, 6 Stage II, 15 Stage III, and 4 Stage IV. Fourteen tumors (32%) were classified as being TP positive. The proportion of Stage I tumors that was TP positive (16%) was significantly lower (P = 0.022) that the corresponding value for Stages II-IV (44%), although the values for microvessel count, AI, and peak systolic velocity (PSV) were similar. AI was significantly lower in TP-positive tumors than in TP-negative tumors (P = 0.015). The PSV was significantly higher in TP-positive tumors (P = 0.02). There was a significant correlation between the microvessel count and the PSV (r = 0.34, P = 0.024). Moreover, AI was significantly inversely related to the PSV (r = 0. 35, P = 0.023). The PSV in a subgroup with a high microvessel count and low AI was significantly higher than that in a subgroup with a low microvessel count and high AI (P = 0.0006). These findings significantly associated with TP expression (P = 0.024).


CONCLUSIONS
The intratumoral PSV, as determined by color Doppler imaging and spectral analysis, might reflect the coordination of angiogenesis and apoptosis associated with TP expression in epithelial ovarian cancer.
Hata
K
K
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, 693-8501, Japan.
Fujiwaki
R
R
Maede
Y
Y
Nakayama
K
K
Fukumoto
M
M
Miyazaki
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002278:Carcinoma in Situ / Q000098:blood supply / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D012039:Regional Blood Flow; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*; D018615:Ultrasonography, Doppler, Color
D013939:Thymidine Phosphorylase