Abstract
Purpose: The thymidine phosphorylase (TP) is a key enzyme involved in the metabolism of pyrimidines. Inhibition or downregulation of this enzyme causes accumulation of metabolites with consequences in DNA replication. TP regulates angiogenesis and chemotactic activity of endothelial cells. Different studies showed the presence of TP upregulation in human cancer but the correlation between TP expression and the microvascular density (MVD) in canine mammary tumors is unknown. The aim of this study was to investigate a possible correlation between the MVD and TP expression in tumor cells of canine mammary tumors of different degree of severity (G1–G3) by immunohistochemical analysis.Methods: Sixty-eight samples of spontaneous mammary neoplasia of 5–12 cm in diameter were collected from purebred and mixed-breed dogs (mean aged = 9.5 ± 7), not subject to chemotherapy treatments in veterinary clinics. Histopathological analysis and immunostaining were performed.Results: Carcinoma simple samples have been classified as 72.06% of tubule-papillary, 20.59% cysto-papillary, and 7.35% tubular carcinomas. Immunostainings revealed a marked cytoplasmic expression of TP in 30.88% of samples, mild in 32.35%, weaker in 22.07%, and negative in 14.70%. The correlation analysis and two-way ANOVA showed a linear correlation between MVD and TP with a coefficient of correlation (r) > 0.5 (p < 0.05) in G2 and G3. No correlation between variables was found in G1.Conclusions: These findings suggest that cytoplasmic TP overexpression is correlated with microvascular density in canine mammary tumors, in severe grade, and it can be a potential prognostic factor in breast cancer.
Highlights
The thymidine phosphorylase (TP) enzyme was purified in the mid-1970s from both Escherichia coli and Salmonella spp. [1]
Considering that the spontaneous mammary tumors of the dogs have a biological and histopathological behavior similar to that of the woman, and that the human TP shares 39% of identity with the prokaryotic one [25], we investigated the role of TP in the canine mammary tumor cells highlighting the immunohistochemical expression patterns correlating them to tissue neovascularization and tumor grade/stage
The frequency-distribution of the number of TP immunostained cells in grade 2 (G2) and grade 3 (G3) were described by a bell-shaped Gaussian distribution curve (Figure 1)
Summary
The thymidine phosphorylase (TP) enzyme was purified in the mid-1970s from both Escherichia coli and Salmonella spp. [1]. The thymidine phosphorylase (TP) enzyme was purified in the mid-1970s from both Escherichia coli and Salmonella spp. This enzyme is encoded by a gene of chromosome 22, in position 13 of the long arm (22q13) and consists of two subunits of 47 kDa in eukaryotic cells (45 kDa in Salmonella spp.). TP activity reduction causes an accumulation of thymidine (dThd) and deoxyuridine (dUrd) in blood and tissues, causing an imbalance in the nucleotide pool. TP is considered to be a homolog of the endothelial platelet factor (PD-ECGF), its function is promoting angiogenesis and the chemotactic activity of endothelial cells [2, 6]
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