The cytosol activity of thymidine phosphorylase in endometrial cancer

Abstract

Background: Thymidine phosphorylase (TP) is identical with platelet-derived endothelial cell growth factor (PD-ECGF) which promotes angiogenesis. The aim of this study was to evaluate the cytosol activity of TP in tumor samples from patients with endometrial cancer.

Methods: The activity of TP was measured by the spectrophotometric method in the cytosol of endometrial tumor samples from 43 patients. Moreover, the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) protein and microvessel density (MD) were examined in the same endometrial tumor samples by immunohistochemical staining. Normal endometrium from 16 women, treated surgically due to nononcological reasons served as a control.A relationship between the cytosol TP activity, PD-ECGF/TP protein expression, MD and clinicopathologic features was investigated.

Results: A significantly higher the cytosol TP activity, PD-ECGF/TP protein expression and MD was stated in malignant tumor samples when compared to the control (samples of normal endometrium). A positive statistically significant correlation between the cytosol enzyme activity and PD-ECGF/TP protein expression and MD was found, but weaker from the remaining ones between PD-ECGF/TP protein expression and MD was observed.Besides no correlation between the cytosol TP activity, PD-ECGF/TP protein expression as well as MD and grading or histopatological type of endometrial cancer was stated.

Conclusion: The cytosol TP activity in endometrial cancer is significantly higher than in normal endometrium, with no relation as to the stage and grade of tumors, but correlates with the PD-ECGF/TP protein expression and MD may therefore be associated with favorable prognosis in patients treated with chemo- or radiotherapy after surgery.

Figure 1

The cytosol TP activity, PD-ECGF/TP – protein expression and microvessel density in tumor (T) and normal endometrium (E). Results are expressed as mean ± SD (standard deviation), p < 0.001. A.) TP activity – The cytosol TP activity measured in micromoles of T × mg protein^-1 × h^-1 as described in Materials and Methods. Tumor samples were from 43 endometrial cancer patients and normal endometrium from 16 women treated surgically due to nononcological reasons. B.) TP/PDECGF – PD-ECGF/TP – protein expression; The extent of immunohistochemical expressions was classified into 0, 1, 2, 3 grades as described in Materials and Methods. C.) MD – Microvessel density. Microvessel counting, performed according to the Weidner's method [24] measured as described in Materials and Methods.

Figure 2

Immunohistochemical staining for PDECGF/TP protein expression in endometrial cancer. Immunohistochemical staining for PD-ECGF/TP protein was performed using the anti-TP mouse monoclonal antibody NCL-PDEGF clone P-GF.44C (NovoCastra) The cytoplasmic and only occasional nuclear staining of cancer cells is seen (note negative squamous metaplastic cells in the center). On the right normal endometrial cells. (200×).

Figure 3

Immunohistochemical staining for PDECGF/TP protein in normal endometrium. Immunohistochemical staining for PD-ECGF/TP protein was performed using the anti-TP mouse monoclonal antibody NCL-PDEGF clone P-GF.44C (NovoCastra) (200×).

Figure 4

Immunohistochemical staining for microvessel density (MD) in endometrial cancer. Microvessel assessment was performed using a mouse anti-human CD31 (Dako) antibody (100×).

Figure 5

The correlation between the cytosol TP activity and expression of PD-ECGF/TP protein in endometrial cancer. p = 0.0035, R = 0.4858, statistical analysis according to Spearman (measured as described in Materials and Methods).

Figure 6

The correlation between the cytosol TP activity and microvessel density (MD) in endometrial cancer. p = 0.0286, R = 0.3649, statistical analysis according to Spearman (measured as described in Materials and Methods).