Prognostic significance of tumour-associated inflammation related markers in canine mammary gland tumours : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterniary Science at Massey University, Manawatū, New Zealand

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Massey University
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Canine mammary gland tumours (CMGTs) are a major cause of illness and premature death in female dogs, especially in countries like Sri Lanka where early de-sexing is not a routine veterinary practice. Therefore, there is a need for prognostic markers which can better predict the behaviour of a CMGT. In human breast cancers (HBCs), some markers of tumour-associated inflammation (TAI) have been shown to better predict prognosis than many conventional prognostic markers. This thesis investigated whether TAI prognostic markers adopted from human breast cancers are similarly prognostic for CMGTs. The prognostic markers investigated in this thesis included tumour stromal mast cell density determined by toluidine blue staining, gene expression of chemokines: CCL5, CXCL12, CXCL10, and chemokine receptors: CXCR3, CXCR4, CXCR7, CCR4, CCR9 and gene expression and immunostaining of two immune checkpoint molecules: programme death ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) . Similar to HBCs, all markers except CXCL10 and CCR4 were prognostic of the disease outcome determined by disease-specific survival times of the dogs with mammary neoplasms. Of them, stromal mast cell density, CCL5 gene expression and PD-L1 immunostaining were prognostic independent of tumour size, tumour histological grade, and lympho-vascular invasion observed in histological sections. In conclusion, this thesis identified that similar to HBCs, TAI related prognostic markers are useful to better predict the behaviour of CMGTs while stromal mast cell density has the potential to be adopted for routine laboratory prognostic determination. In addition to identification of prognostic markers, surveys of CMGTs in Sri Lanka and New Zealand conducted for sample collection gathered large amounts of information that allowed a comparison of CMGTs between the two countries. These studies allowed a determination of the characteristics of dogs with CMGTs, as well as allowing histological characterisation of the tumours within the two countries.
Dogs, Diseases, Mammary glands, Tumors, Prognosis, Sri Lanka, New Zealand, Tumor markers