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Introduction: The main adaptive immune cells are T and B lymphocytes and they play key roles in the induction of immune responses against canine mammary tumours. Investigating these cell subpopulations may lead to more precise diagnosis of these malignancies. Material and Methods: The percentages of CD3+, CD4+ and CD8+ T cells and of CD21+ B cells in the peripheral blood of bitches with malignant mammary tumours were compared with those in the blood of healthy animals. The phenotypic features of peripheral blood leukocytes were evaluated by flow cytometry. Results: There was a significant difference in the mean percentages of CD3+ lymphocytes between healthy (66.7%) and metastatic dogs (46.1%), and between tumour-bearing non-metastatic (66.6%) and metastatic dogs. There was also a significant difference in CD4+ T helper cell percentages between healthy dogs (40.4%) and dogs with metastases (23.2%), and between the latter and dogs without them (35.5%). In the case of CD21+ lymphocyte subsets, a significant difference was noted between healthy animals (10.9%) and those with metastases (20.1%), and between the latter and patients without metastases (8.5%). There were also significant differences in CD3+/CD21+ ratios between the group with metastases (3.0), the healthy group (7.8), and the group without metastases (8.5). Similarly, a significant difference was noted in CD4+/CD8+ ratios between animals with metastases (1.4), bitches in the control group (2.2), and dogs without metastases (1.9). Conclusion: Peripheral blood leukocyte phenotypic characteristics are putative novel biomarkers. These findings may be useful in future studies improving mammary tumour diagnostic procedures, especially in metastasis detection.

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Inflammation is a frequent finding in feline mammary neoplasms. Recent research suggests that the presence and location of tumour-associated immune cells might play a significant role in the clinical outcome of feline mammary carcinomas. The present study aimed to characterise the overall inflammatory infiltrates in healthy, hyperplastic/dysplastic, benign and malignant lesions of the feline mammary gland, and to evaluate its association with clinicopathological features. Perilesional and intralesional inflammatory foci were evaluated in 307 lesions from 185 queens, and categorised according to its distribution and intensity. The presence, location and density of tertiary lymphoid structures were also assessed. A control group included 24 queens without mammary changes. The presence of intralesional and perilesional inflammatory infiltrate was observed in a majority of the lesions (80.8% and 90.2%, respectively), but differed according to the type of mammary lesion, being more remarkable in malignant neoplasms. Only scarce individual cells were observed in 28.1% of the normal mammary glands. Data analysis revealed statistically significant associations (p < 0.05) between the presence of a more prominent intralesional and perilesional inflammatory reaction and several clinicopathological features associated with worse prognosis, including clinical stage, tumour size, mitotic count, lymphovascular invasion and lymph node metastasis. Furthermore, tertiary lymphoid structures were significantly more frequent in tumours with an infiltrative growth and lymph node metastasis. According to our results, the inflammatory reaction present in different types of feline mammary lesions is associated with the development of more aggressive tumours.

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ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a major cause of death among human females across the globe. The anti-neoplastic agents or therapies used for the treatment of cancers can enhance longevity but are subsequently observed to deteriorate the quality of life due to the extensive side effects produced. Saussurea costus is a potential medicinal plant of the Himalayas with noticeable ethnopharmacological properties. The phytochemicals present in Saussurea costus are responsible for anti-carcinogenic potential and warranted nil or minimal side effects of Saussurea costus and directed to use this plant as a preventive or therapeutic drug candidate against cancers. AIM OF THE STUDY: The present study was planned to evaluate the anti-neoplastic activity of Saussurea costus root extract (SL) in rat mammary tumour model. MATERIALS AND METHODS: The anti-neoplastic activity of SL root extract at 3 different doses (100, 250 and 500 mg/kg BW) for 18 weeks against 12-dimethylbenz (a) anthracene (DMBA)-induced mammary tumours in Sprague Dawley (SD) female rats was analyzed through serum biochemistry (ALT, AST, ALP, Total protein, Creatinine and BUN), oxidative stress parameters (Lipid peroxidation, Catalase and Reduced glutathione), pro-inflammatory cytokines (TNF-α and NF-κB), immunohistochemical markers (Ki-67, MMP-9 and VEGF), real-time PCR (PCNA, p53, bax, bcl-2 and caspase-3, genes) and molecular docking. RESULTS: Inhibition of tumour parameters, minimal alteration in the liver (ALT, AST and ALP) and kidney enzymes (Creatinine and BUN), decreased activity of MDA, elevated levels of GSH and catalase, reduction in the levels of pro-inflammatory cytokines i.e. TNF-α and NF-κB, reduced gross and histomorphological changes, declined expression of Ki-67, MMP-9 and VEGF in vivo rat model, mRNA expression of cancer-related genes and docking of dehydrocostus lactone and costunolide with NF-κB and TNF-α demonstrated the chemopreventive action of SL root extract. CONCLUSIONS: The in-vivo trial elucidates anti-neoplastic activity of Saussurea costus root extract as demonstrated through the reduction of biochemical indices, oxidative stress parameters, histological changes, pro-inflammatory cytokines (NF-κB and TNF-α), cellular proliferation (Ki-67), metastases (MMP-9) and neovascularization (VEGF) markers with highest anti-neoplastic effect of SL extract at the dose of 500 mg/kg body weight. Therefore, the present study signifies the need to use the active principles present in the root extract of Saussurea costus against breast cancer as a therapeutic regimen.

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Introduction: The development of genetic research over recent decades has enabled the discovery of new genetic markers, such as single nucleotide polymorphisms (SNPs). This, as well as the full sequencing of the dog genome, has enabled genome-wide association studies (GWAS) to be used in the search for genetic causes of canine mammary tumours (CMTs). Material and Methods: Genotypic data containing 175,000 SNPs, which had been obtained using the Illumina CanineHD BeadChip microarray technique, were available for analysis in this study. The data concerned 118 bitches, including 36 animals with CMT, representing various breeds and age groups. Statistical analysis was performed in two steps: quality control of genotyping data and genome-wide association analysis based on dominant, recessive, overdominant, codominant, and log-additive models with the single SNP effects. Results: A total of 40 different SNPs significantly associated with CMT appearance were detected. Moreover, twelve SNPs showed statistical significance in more than one model. Of all the significant SNPs, two, namely BICF2G630136001 in the overdominant model and TIGRP2P107898_rs9044787 in the log-additive model, reached the 5-8 significance level. The other SNPs were significant to a 1-5 level. Conclusion: In the group of SNPs indicated as significant in the GWAS analysis, several transpired to be localised within genes that may play an important role in CMT.

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The aim of the study was to compare the immunohistochemical expression of topoisomerase IIα protein (Topo IIα) with Ki67 expression and mitotic count in feline mammary carcinomas (FMCs). Topo IIα is considered as a proliferation indicator as well as a molecular target of anthracycline chemotherapy. The studied material included 70 FMCs from female cats treated with mastectomy. Primary mouse monoclonal antibodies directed against Topo IIα and Ki67 were used in immunohistochemical reactions. The number of mitotic figures was counted at 400× magnification in a field of 2.37 mm2. Immunohistochemical reaction for Topo IIα occurred in cell nuclei. The Topo IIα index ranged from 6.12% to 54.60% and was positively correlated with the values of the Ki67 index (r = 0.7193) and the mitotic count (r = 0. 2858). This indicates the potential possibility of use of the immunohistochemical expression of Topo IIα to assess the rate of proliferation in FMCs. The wide range of expression of Topo IIα in individual tumorus found in the conducted studies allows us to hypothesize that its assessment could be used as a predictive marker in chemotherapy of FMCs with the use of anthracyclines. However, this requires confirmation in clinical trials.

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The aim of this study was to evaluate the plasma levels of chemokines CCL2 and CXCL12 in female dogs with malignant mammary gland tumours without and with metastases. The concentrations of CCL2 and CXCL12 were determined in 25 female dogs with malignant mammary gland tumours (15 without metastases and 10 with metastases) and 10 healthy control animals using a specific canine ELISA assay. The mean plasma concentrations of CCL2 and CXCL12 were significantly higher (p<0.05) in the metastatic group compared to the control group. Moreover, the concentrations of these chemokines were markedly higher in the dogs with metastases than in those without metastases; however, a statistically significant difference was not found. The concentrations of both tested chemokines were numerically increased in the dogs with grade 2 and grade 3 carcinomas compared to the dogs with grade 1 carcinomas but the differences did not reach statistical significance. In conclusion, the results of our study demonstrate that plasma concentrations of chemokines CCL2 and CXCL12 are significantly increased in the dogs with metastatic malignant mammary gland tumours compared to the healthy dogs and show an upward trend compared to those without metastases. However, clarifying whether the increase of these chemokines is a cause or an effect of metastasis in female dogs with malignant mammary gland tumours as well as their potential role in metastatic process requires further research.

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The Hippo signalling pathway is involved in breast cancer and canine mammary tumour (CMT). This study sought to evaluate the efficacy of fluvastatin on the Hippo pathway and its main effectors, YAP and TAZ, in vivo in a murine CMT cell line xenograft model. On treatment day 1, mice were divided into four groups: vehicle, fluvastatin, doxorubicin or a combination therapy. Tumour volumes were monitored with callipers and tissues harvested on day 28th of treatment. Histopathological examination of tumour tissues and major organs was performed as well as tumour evaluation of necrosis, apoptosis, cellular proliferation, expression of YAP, TAZ and the mRNA levels of four of their target genes (CTGF, CYR61, ANKRD1 and RHAMM2). Results showed a statistically significant variation in tumour volumes only for the combination therapy and final tumour weight only for the doxorubicin group compared to control. There was no significant difference in tumour necrosis, expression of CC3, ki-67, YAP and TAZ measured by immunohistochemistry and in the mRNA levels of the target genes. Unexpectedly, lung metastases were found in the control group (9) and not in the fluvastatin treated group (7). In addition, mass spectrometry-based quantification of fluvastatin reveals concentrations comparable to levels reported to exert therapeutic effects. This study shows that fluvastatin tumours concentration reached therapeutic levels without having an effect on the hippo pathway or various tumour parameters. Interestingly, only the control group had lung metastases. This study is the first to explore the repurposing of statins for cancer treatment in veterinary medicine.

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BACKGROUND: Canine mammary tumours (CMTs) are the most frequent tumours in intact female dogs and show strong similarities with human breast cancer. In contrast to the human disease there are no standardised diagnostic or prognostic biomarkers available to guide treatment. We recently identified a prognostic 18-gene RNA signature that could stratify human breast cancer patients into groups with significantly different risk of distant metastasis formation. Here, we assessed whether expression patterns of these RNAs were also associated with canine tumour progression. METHOD: A sequential forward feature selection process was performed on a previously published microarray dataset of 27 CMTs with and without lymph node (LN) metastases to identify RNAs with significantly differential expression to identify prognostic genes within the 18-gene signature. Using an independent set of 33 newly identified archival CMTs, we compared expression of the identified prognostic subset on RNA and protein basis using RT-qPCR and immunohistochemistry on FFPE-tissue sections. RESULTS: While the 18-gene signature as a whole did not have any prognostic power, a subset of three RNAs: Col13a1, Spock2, and Sfrp1, together completely separated CMTs with and without LN metastasis in the microarray set. However, in the new independent set assessed by RT-qPCR, only the Wnt-antagonist Sfrp1 showed significantly increased mRNA abundance in CMTs without LN metastases on its own (p = 0.013) in logistic regression analysis. This correlated with stronger SFRP1 protein staining intensity of the myoepithelium and/or stroma (p < 0.001). SFRP1 staining, as well as ß-catenin membrane staining, was significantly associated with negative LN status (p = 0.010 and 0.014 respectively). However, SFRP1 did not correlate with ß-catenin membrane staining (p = 0.14). CONCLUSION: The study identified SFRP1 as a potential biomarker for metastasis formation in CMTs, but lack of SFRP1 was not associated with reduced membrane-localisation of ß-catenin in CMTs.

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Canine mammary tumours (CMTs) are the most common cancer in intact female dogs. In addition to surgery, additional targeted and non-targeted therapies may offer survival benefits to these patients. Therefore, exploring new treatments for CMT is a promising area in veterinary oncology. CMT cells have an altered lipid metabolism and use the oxidation of fatty acids for their energy needs. Here we investigated the tumoricidal effects of teglicar, a reversible inhibitor of carnitine palmitoyl transferase 1A (CPT1A), the rate-limiting enzyme for fatty acid import into mitochondria, on two CMT cells, P114 and CMT-U229. Viability and apoptosis were examined in CMT cells using the crystal violet assay, trypan blue assay, and flow cytometry analysis. The expression of mediators of apoptosis signalling (e.g., caspase-9, caspase-8, and caspase-3) was assessed by quantitative real-time polymerase chain reaction and western blot analyses. Teglicar was able to decrease cell viability and induce apoptosis in P114 and CMT-U229 cells. At the molecular level, the effect of teglicar was associated with an upregulation of the mRNA expression levels of caspase-9, caspase-8, and caspase-3 and an increase in their protein levels. In summary, our results show that teglicar has a potential effect against CMTs through the induction of apoptotic cell death, making it a promising therapeutic agent against CMTs.

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The idea of using tumour biomarkers as diagnostic tools is progressively increasing. Of these, serum biomarkers are of particular interest, as they can provide rapid results. In the present study, serum samples from 26 bitches diagnosed with mammary tumours, plus 4 healthy bitches, were obtained. The samples were analysed using CD antibody microarrays targeting 90 CD surface markers and 56 cytokines/chemokines. A total of five CD proteins, namely CD20, CD45RA, CD53, CD59, and CD99, were selected and further analysed, utilizing immunoblotting techniques to validate the microarray results. CD45RA showed a significantly lower abundance in the serum samples from the bitches carrying mammary neoplasia in comparison to the healthy animals. Regarding CD99, the serum samples from the neoplastic bitches showed it in a significantly higher abundance than those from the healthy patients. Finally, CD20 showed a significantly higher abundance in bitches carrying a malignant mammary tumour in comparison to healthy patients, but no differential expression between malignant and benign tumours was observed. According to these results, both CD99 and CD45RA are indicators of mammary tumour presence, but without distinguishing between malignant and benign.

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BACKGROUND: Canine mammary tumours (CMTs) are the most common neoplasm appearing in female dogs and are considered the equivalent animal model of human breast cancer. However, in the literature, there is a gap for ultrasonic characterisation of these tumours. In this study, experimental measurements for acoustic attenuation and propagation speed of three surgically excised malignant CMTs were implemented. METHODS: The three tumours were fixed in formaldehyde for up to 72 h and a total of five sample pieces were sectioned from the three tumours to account for the varied morphology observed along the tumours. The through-transmission and pulse-echo techniques were employed for experimental measurements of the acoustic attenuation and propagation speed. RESULTS: Acoustic propagation speed of the five samples as measured at 2.7 MHz was in the range of 1568-1636 m/s. Correspondingly, acoustic attenuation was in the range of 1.95-3.45 dB/cm.MHz. Variations in both speed and attenuation were observed between samples acquired from the same tumour. CONCLUSIONS: Present findings suggest that both acoustic attenuation and propagation speed of CMTs are higher than normal canine tissues due to increased heterogeneity and varied morphology visually observed between the tumour specimens and evidenced by histological examination. Nevertheless, experimental results could aid in enhancing the use of ultrasound in the diagnosis and treatment of CMTs as well as provide essential data for comparative oncology.

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Histological diagnosis of Canine Mammary Tumours (CMTs) provides the basis for proper treatment and follow-up. Nowadays, its accuracy is poorly understood and variable interpretation of histological criteria leads to a lack of standardisation and impossibility to compare studies. This study aimed to quantify the reproducibility of histological diagnosis and grading in CMTs. A blinded ring test on 36 CMTs was performed by 15 veterinary pathologists with different levels of education, after discussion of critical points on the Davis-Thompson Foundation Classification and providing consensus guidelines. Kappa statistics were used to compare the interobserver variability. The overall concordance rate of diagnostic interpretations of WP on identification of hyperplasia-dysplasia/benign/malignant lesions showed a substantial agreement (average k ranging from 0.66 to 0.82, with a k-combined of 0.76). Instead, outcomes on ICD-O-3.2 morphological code /diagnosis of histotype had only a moderate agreement (average k ranging from 0.44 and 0.64, with a k-combined of 0.54). The results demonstrated that standardised classification and consensus guidelines can produce moderate to substantial agreement; however, further efforts are needed to increase this agreement in distinguishing benign versus malignant lesions and in histological grading.

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In this study plasma concentrations of IL-1α and IL-8 in 29 female dogs with malignant mammary gland tumours (19 without metastasis and 10 with metastasis) and in 10 healthy control animals were determined. Concentrations of IL-1α and IL-8 were analysed using a specific canine ELISA assay. Mean plasma concentrations of IL-1α and IL-8 were significantly higher (p⟨0.05) in female dogs with both non-metastatic and metastatic malignant tumours compared to the healthy animals. The concentrations of both tested cytokines were significantly increased (p⟨0.05) in the dogs with metastasis. In female dogs with mammary carcinomas, the plasma concentration of IL-1α was significantly higher (p⟨0.05) in the animals with grade 3 tumours compared to the dogs with grade 1 tumours. The concentration of IL-8 was significantly higher (p⟨0.05) in the dogs with grade 3 tumours compared to that found in the animals with grade 1 and grade 2 tumours. A moderate correlation (r=0.433) was found between IL-1α and IL-8 concentrations in the female dogs. These findings suggest that increased malignancy and invasiveness of canine mammary tumours is associated with an increased production of IL-1α and IL-8 in the tumour microenvironment, which, in turn, leads to an increase in their circulating levels. This may indicate that circulating levels of the cytokines investigated could be considered as diagnostic and prognostic markers in canine malignant mammary tumours. However, further studies in this fields are needed.

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BACKGROUND: Mammary tumor is one of the most common diseases of canine in pet clinics. OBJECTIVES: This study investigates the distribution and expression of the tumor transcription factor GLI1 and the downstream proteins, Bmi1 and Sox2, in canine mammary tumors and paracancerous tissues. METHODS: Cancerous and paracancerous normal mammary tissues were detected using western blotting (WB), and immunohistochemistry. RESULTS: The results showed that the histopathology of different types in mammary tumors by microscopic observation. GLI1/Bmi1/Sox2 expression was significantly higher in canine mammary invasive carcinoma than in ductal carcinoma and adjacent normal mammary tissues (p < 0.01). The expression of GLI1 in invasive carcinoma tissues was significantly higher than Bmi1 and Sox2, while Sox2 expression in ductal carcinoma tissues was significantly higher than GLI1 and Bmi1 (p < 0.01). GLI1/Bmi1/Sox2 all showed positive reactions in both mammary tumor and adjacent normal mammary tissues with immunohistochemistry. GLI1 and Sox2 showed strong positive staining in the cytoplasm of invasive mammary carcinoma and ductal carcinoma cells, and weak positive staining in the nuclei. The positive Bmi1 reaction was mainly concentrated in the cytoplasm of invasive carcinoma and ductal carcinoma cells, while the positive reaction on the cell membrane was weak. CONCLUSIONS: We speculate that GLI1 and related proteins play an important role in regulating the proliferation and differentiation of tumors. Therefore, it provides important reference for the pathogenesis and pathogenicity of canine mammary tumor.

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BACKGROUND: Mast cell density has been shown to have both enhancing and inhibiting effects on tumour progression and the ability to predict breast cancer behaviour in humans. However, prognostic results have been contradictory. Some previous studies suggested involvement of mast cells in the progression of canine mammary tumours. This study investigated total, intratumoural and peritumoural mast cell densities by Giemsa staining, and their association with clinicopathological parameters and the disease outcome of canine mammary tumours. In addition, since mast cells promote angiogenesis, the microvascular density and endothelial area were evaluated by CD31 immunostaining. RESULTS: Intratumoural mast cell density was associated with tumour size, lymph node involvement and tumour-infiltrating lymphocyte count, while peritumoural mast cell density was associated with grade. The endothelial area was associated with grade, mitotic index, tubular formation and proliferation index. Tumours with a high grade, high total intratumoural mast cell density and a larger endothelial area were associated with shorter disease-free survival. Intratumoural mast cell density and grade were found to be independent prognostic factors. CONCLUSIONS: These results suggest that intratumoural mast cell density and the endothelial area can be used to evaluate the aggressiveness of canine mammary carcinomas, while intratumoural mast cell density could be of use as an independent predictor of a prognosis of disease-free survival. Peritumoural mast cell density does not seem to influence tumour behaviour.

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Numerous studies have shown that the occurrence and development of tumours are associated with the expression of circular RNAs (circRNAs). However, the expression profile and clinical significance of circRNAs in canine mammary tumours remain unclear. In this paper, we collected tissue samples from three dogs with canine mammary tumours and analysed the expression profiles of circRNAs in these samples using high-throughput sequencing technology. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses revealed 14 biological processes associated with these genes, and 11 of these genes were selected for qRT-PCR to verify their authenticity. CircRNAs have sponge adsorption to miRNAs, so we constructed a circRNA-miRNA network map using Cytoscape software. As a result, we identified a total of 14,851 circRNAs in canine mammary tumours and its adjacent normal tissues. Of these, 106 were differentially expressed (fold change ≥ 2, p ≤ 0.05), and 64 were upregulated and 42 were downregulated. The GO analysis revealed that the biological processes involved were mainly in the regulation of the secretory pathway, the regulation of neurotransmitter secretion and the positive regulation of phagocytosis. Most of these biological pathways were associated with the cGMP-PKG (cyclic guanosine monophosphate) signalling pathway, the cAMP (cyclic adenosine monophosphate) signalling pathway and the oxytocin signalling pathway. After screening, source genes closely associated with canine mammary tumours were found to include RYR2, PDE4D, ROCK2, CREB3L2 and UBA3, and associated circRNAs included chr27:26618544-26687235-, chr26:8194880-8201833+ and chr17:7960861-7967766-. In conclusion, we reveals the expression profile of circRNAs in canine mammary tumours. In addition, some circRNAs might be used as potential biomarkers for molecular diagnosis.

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BACKGROUND: Mastectomy is the most common procedure for treatment of mammary tumours. Dogs undergoing mastectomy have a risk of developing surgical site infections (SSI) and other postoperative complications. However, potential risk factors associated with such complications have been sparsely investigated. Thus, the objective of this retrospective study was to determine the incidence of, and identify risk factors for, SSI and non-SSI postoperative complications after mastectomy performed without perioperative antimicrobial prophylaxis in privately owned otherwise clinically healthy dogs. RESULTS: Medical records were reviewed retrospectively for 135 client-owned female dogs, 10-35 kg in weight and three to 10 years of age, which had undergone mastectomy due to mammary tumours at three referral animal hospitals in Sweden over a 3-year period. Twelve (8.9%) dogs developed SSI, and 21 dogs (17.1%) dogs suffered a non-SSI postoperative complication. The incidence of SSI and all complications (SSI and non-SSI) were higher in dogs that had two to three (SSI: P = 0.036 and all complications: P = 0.0039) and four to five (SSI and all complications: P = 0.038) mammary glands excised, compared to dogs that had one mammary gland excised. The incidence of SSI was 1.7% (n = 1/60) in dogs that had one gland removed. The incidence of non-SSI postoperative complications was higher in dogs with a higher body weight (P = 0.02). CONCLUSIONS: The incidence of SSI was lower than or similar to previously reported incidences of SSI in dog populations that have undergone tumour excisional surgery, despite the fact that dogs in the present study had not received perioperative antibiotics. Dogs that had two or more glands excised had an increased risk of developing SSI and non-SSI complications compared to dogs that had one gland excised. Furthermore, higher BW was associated with an increased risk of non-SSI complications. Results from the study indicate that routine use of perioperative antibiotics in tumour excisional surgery can be questioned, at least in single gland mastectomy in otherwise clinically healthy dogs.

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Among the innate and adaptative immune cells recruited to the tumour site, tumour associated macrophages (TAMs) are particularly abundant and by simplified classification can be classified into (M1) and (M2) TAMs. In the present study, we quantified by immunohistochemistry ionized calcium binding adaptor molecule 1 (Iba1)-positive total and CD204-positive M2-polarized TAMs in 60 canine malignant mammary tumours (CMMTs) to analyze the relationship between M1 or M2 response and the histopathologic features of examined CMMTs, the dogs' body condition score (BCS) and the progression of the neoplastic disease. The mean number of total and CD204+ TAMS were significantly higher in solid and in grade III than in grades I and II carcinomas. Moreover, the mean number of CD204-positive TAMs was significantly higher in CMMTs with lymphatic invasion and necrosis rather than CMMTs without. The presence of higher number of CD204-positive M2-polarized TAMs was associated with a worst outcome of the neoplastic disease: bitches bearing CMMTs with a prevalent M2-polarized TAM response had a median cancer-specific survival time of 449 days, while in animals with a M1-polarized TAM response the median cancer-specific survival time was 1209 days. The results of our study confirm that in CMMTs the presence of a M2-polarized TAMs response might affect the tumour development and behaviour. Finally, it strongly suggests the potential of CD204 expression as a prognostic factor.

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Blood leukocyte counts and respective derived ratios have been described as potential prognostic markers in several tumours in veterinary oncology. This study aimed to evaluate peripheral blood leukocyte subpopulations and neutrophil-to-lymphocyte ratio (NLR) as prognostic factors for feline mammary carcinomas (FMC). Medical records from cats diagnosed with FMC between 2017 to 2019 were reviewed. Cats were included if fully staged, classified as WHO stage I to III, and submitted to mastectomy. Cats were excluded if they had evidence of other diseases. Forty-nine cats were included. The study endpoints were disease-free interval (DFI) and tumour-specific survival (TSS). The median DFI and TSS were 389 days and 528 days respectively. In the univariate analysis, higher values of total white blood cell count (WBC), neutrophil count (NEU) and NLR were identified as significant prognostic factors for both endpoints (P < .05). On the multivariate analysis, NLR remained an independent prognostic factor for TSS (P = .024). In the receiver operating characteristic curve analysis, the estimated cut-off for WBC was 8.49 × 109 /L (DFI and TSS); for NEU was 4.62 × 109 /L (DFI) and 6.65 × 109 /L (TSS) and for NLR was 2.46. These cut-offs were significant prognostic factors for DFI and TSS (P < .05). NLR cut-off remained an independent prognostic factor for both DFI (P = .032) and TSS (P = .043) in the multivariable analysis. Our results suggest that NLR, NEU, and WBC can be important non-invasive presurgical prognostic markers, and that NLR is an independent prognostic marker for FMC. Prospective studies are warranted to validate its clinical use.

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This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose doxorubicin or surgery alone in cats with mammary carcinoma. Medical records of 228 female cats treated for mammary carcinoma between 2008 and 2018, were reviewed in eight veterinary institutions. Only cats with complete tumour staging and radical mastectomy were included in the study. One hundred and thirty-seven cats were divided into three treatment groups: group 1 (n = 80) cats treated with surgery, group 2 (n = 34) cats that had surgery and adjuvant treatment with doxorubicin, and group 3 (n = 23) cats with surgery and adjuvant treatment with low dose metronomic cyclophosphamide and meloxicam. The study endpoints were disease free interval (DFI) and overall survival (OS). Toxicity was evaluated according to the VCOG-CTCAE criteria. The median DFI was 270, 226 and 372 days in groups 1, 2 and 3, respectively. The median OS was 338 (group 1), 421 (group 2) and 430 (group 3) days. The differences between groups were not significant (DFI P = .280 and OS P = .186). Toxicity was observed in 52.9% (n = 18) of cats in group 2 and 39.1% (n = 9) of cats in group 3, with mild to moderate intensity. Differences were not significant (P = .306). In conclusion, adjuvant chemotherapy treatment did not improve survival and the overall benefit remains unproven. Randomized prospective trials are necessary to clarify the effectiveness of adjuvant chemotherapy treatment for feline mammary carcinomas.

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