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犬乳腺肿瘤中胸苷磷酸化酶表达与微血管密度的相关性分析：乳腺癌可能的预后因素

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

作者信息

Zizzo Nicola, Passantino Giuseppe, D'alessio Roberta Maria, Tinelli Antonella, Lopresti Giuseppe, Patruno Rosa, Tricarico Domenico, Maqoud Fatima, Scala Rosa, Zito Francesco Alfredo, Ranieri Girolamo

机构信息

Section of Veterinary Pathology and Comparative Oncology, Department of Veterinary Medicine, University of Bari "Aldo Moro", Valenzano, Italy.

MD Freelancer, Bristol, United Kingdom.

出版信息

Front Vet Sci. 2019 Oct 25;6:368. doi: 10.3389/fvets.2019.00368. eCollection 2019.

DOI:10.3389/fvets.2019.00368
PMID:31709268
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6823610/
Abstract

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. 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. 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 () > 0.5 ( < 0.05) in G2 and G3. No correlation between variables was found in G1. 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.

摘要

胸苷磷酸化酶（TP）是参与嘧啶代谢的关键酶。该酶的抑制或下调会导致代谢产物积累，进而影响DNA复制。TP可调节内皮细胞的血管生成和趋化活性。不同研究表明，TP在人类癌症中存在上调现象，但TP表达与犬乳腺肿瘤微血管密度（MVD）之间的相关性尚不清楚。本研究旨在通过免疫组织化学分析，探讨不同严重程度（G1 - G3）的犬乳腺肿瘤细胞中MVD与TP表达之间的可能相关性。从纯种和混种犬（平均年龄 = 9.5 ± 7岁）收集了68个直径为5 - 12 cm的自发性乳腺肿瘤样本，这些犬未在兽医诊所接受过化疗治疗。进行了组织病理学分析和免疫染色。单纯癌样本中，小管乳头状癌占72.06%，囊状乳头状癌占20.59%，管状癌占7.35%。免疫染色显示，30.88%的样本中TP呈明显的细胞质表达，32.35%为轻度表达，22.07%为较弱表达，14.70%为阴性表达。相关性分析和双向方差分析显示，在G2和G3中，MVD与TP之间存在线性相关性，相关系数（）> 0.5（< 0.05）。在G1中未发现变量之间的相关性。这些发现表明，在严重程度较高的犬乳腺肿瘤中，细胞质TP过表达与微血管密度相关，它可能是乳腺癌的一个潜在预后因素。

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