Expression of thymidine phosphorylase in malignant ovarian tumors: correlation with microvessel density and an ultrasound-derived index of angiogenesis.

Abstract

The aim of this study was to determine whether the expression of thymidine phosphorylase by ovarian cancer cells correlates with the density of microvessels within the tumor, and with ultrasound-derived indices of blood flow. Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using monoclonal antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were positive or negative for thymidine phosphorylase, the microvessel count and the peak systolic velocity (PSV). Forty-two tumors were studied (three of low malignant potential, 29 epithelial, four granulosa cell, two germ cell and four metastatic); 18 were stage I, six stage II, 11 stage III and three stage IV. Twenty-seven tumors (64%) were classified as thymidine phosphorylase-positive. The proportion of stage I tumors that was thymidine phosphorylase-positive (44%) was significantly lower (p = 0.022) than the corresponding value for stages II-IV (85%), but the values for microvessel count and PSV were similar. The microvessel count in thymidine phosphorylase-positive tumors was significantly higher than in thymidine phosphorylase-negative tumors (p = 0.005). Similarly, the PSV was significantly higher in thymidine phosphorylase-positive tumors (p = 0.009). There was a significant correlation between the microvessel count and the PSV (r = 0.354, p = 0.022). The expression of thymidine phosphorylase by malignant tumor cells is associated with an increase in microvessel density and PSV in patients with ovarian cancer.