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Front. Vet. Sci. | doi: 10.3389/fvets.2019.00368

Thymidine Phosphorylase Expression and Microvascular Density Correlation Analysis in Canine Mammary Tumor: Possible Prognostic Factor in Breast Cancer

 Nicola Zizzo1*,  Giuseppe Passantino1, Roberta D'alessio2,  Antonella Tinelli1, Giuseppe Lopresti1, Rosa Patruno1,  Domenico Tricarico3, 4*, Fatima Maqoud4,  Rosa Scala4, Francesco A. Zito5 and Girolamo Ranieri5
  • 1Department of Veterinary Medicine, University of Bari Aldo Moro, Italy
  • 2Independent researcher, United Kingdom
  • 3University of Bari Aldo Moro, Italy
  • 4Department of Pharmacy and Pharmaceutical Sciences, University of Bari Aldo Moro, Italy
  • 5Istituto Tumori Giovanni Paolo II (IRCCS), Italy

Purpose: The thymidine phosphorylase (TP) is a key enzyme involved in the metabolism of pyrimidines. Inhibition or downregulation of this enzyme causes accumulation of me-tabolites with consequences in DNA replication. TP regulates angiogenesis and chemo-tactic activity of endothelial cells. Different studies showed the presence of TP upregula-tion 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 in-vestigate 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: 68 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% cystic​-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.

Keywords: Canine mammary cancer, Thymidine phosphorylase (TP), Histopahology, microvasculature, Cell Proliferation

Received: 06 Aug 2019; Accepted: 04 Oct 2019.

Copyright: © 2019 Zizzo, Passantino, D'alessio, Tinelli, Lopresti, Patruno, Tricarico, Maqoud, Scala, Zito and Ranieri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Nicola Zizzo, Department of Veterinary Medicine, University of Bari Aldo Moro, Valenzano, Italy, nicola.zizzo@uniba.it
Prof. Domenico Tricarico, University of Bari Aldo Moro, Bari, Italy, dtricarico@farmbiol.uniba.it