Consensus Proposal on Essential Phenotype Markers and Hormone Receptor Assessment in Canine Mammary Tumours

Peña, Laura; Gama, Adelina; Goldschmidt, Michael H.; Abadie, Jérôme; Benazzi, Cinzia; Castagnaro, Massimo; Díez, Lucía; Gärtner, Fátima; Hellmén, Eva; Kiupel, Matti; Millán, Y.; Miller, Margaret A.; Nguyen, Françoise; Poli, Alessandro; Sarli, Giuseppe; Zappulli, Valentina; Mulas, J. Martı́n de las

doi:10.1016/j.jcpa.2013.11.041

Cited by 23 publications

(59 citation statements)

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“…The immunoexpression of ERα was evaluated semi-quantitatively according to the Allred scoring system [ 35 ]. Briefly, the Allred score (total score, TS) is the sum of the percentage of stained cells (PS) and the intensity of immunolabeling (IS).…”

Section: Methodsmentioning

confidence: 99%

Epigenetics in Canine Mammary Tumors: Upregulation of miR-18a and miR-18b Oncogenes Is Associated with Decreased ERS1 Target mRNA Expression and ERα Immunoexpression in Highly Proliferating Carcinomas

Abbate

Arfuso

Riolo³

et al. 2023

Animals

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The expression of miRNAs is one of the main epigenetic mechanisms responsible for the regulation of gene expression in mammals, and in cancer, miRNAs participate by regulating the expression of protein-coding cancer-associated genes. In canine mammary tumors (CMTs), the ESR1 gene encodes for ERα, and represents a major target gene for miR-18a and miR-18b, previously found to be overexpressed in mammary carcinomas. A loss in ERα expression in CMTs is commonly associated with poor prognosis, and it is noteworthy that the downregulation of the ESR1 would appear to be more epigenetic than genetic in nature. In this study, the expression of ESR1 mRNA in formalin-fixed, paraffin-embedded (FFPE) canine mammary tumors (CMTs) was evaluated and compared with the expression levels of miR18a and miR18b, both assessed via RT-qPCR. Furthermore, the possible correlation between the miRNA expression data and the immunohistochemical prognostic factors (ERα immunoexpression; Ki67 proliferative index) was explored. A total of twenty-six FFPE mammary samples were used, including 22 CMTs (7 benign; 15 malignant) and four control samples (three normal mammary glands and one case of lobular hyperplasia). The obtained results demonstrate that miR-18a and miR-18b are upregulated in malignant CMTs, negatively correlating with the expression of target ESR1 mRNA. Of note, the upregulation of miRNAs strictly reflects the progressive loss of ERα immunoexpression and increased tumor cell proliferation as measured using the Ki67 index. The results suggest a central role of miR-18a and miR-18b in the pathophysiology of canine mammary tumors as potential epigenetic mechanisms involved in ERα downregulation. Moreover, as miRNA expression reflects ERα protein status and a high proliferative index, miR-18a and miR-18b may represent promising biomarkers with prognostic value. More detailed investigations on a larger number of cases are needed to better understand the influence of these miRNAs in canine mammary tumors.

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Section: Methodsmentioning

confidence: 99%

Epigenetics in Canine Mammary Tumors: Upregulation of miR-18a and miR-18b Oncogenes Is Associated with Decreased ERS1 Target mRNA Expression and ERα Immunoexpression in Highly Proliferating Carcinomas

Abbate

Arfuso

Riolo³

et al. 2023

Animals

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“…Primary antibody was replaced with an irrelevant, isotype-matched antibody as a negative control. Sections of normal feline mammary gland and feline mammary carcinoma score 3+ 24,33 were used as controls to assess the specificity of the IHC procedure.…”

Section: Methodsmentioning

confidence: 99%

“…Evaluation of HER2 protein IHC expression was recorded by 2 methods: The 2013 recommendations of the ASCO/CAP for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer 33 The standard guidelines proposed for HER2 IHC evaluation in canine mammary tumors 24 …”

Section: Methodsmentioning

confidence: 99%

“…Cases with no labeling (0) or weak, incomplete membrane labeling (1+) in any percentage of cells are considered negative. 24…”

Section: Methodsmentioning

confidence: 99%

“…3,5,7,17,25,28 The standard guidelines for HER2 evaluation in canine mammary tumor propose considering positive cases as only those with a 3+ score by immunohistochemistry (IHC). 24 In humans, based on the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, equivocal IHC cases (2+) are subjected to fluorescence in situ hybridization (FISH) analysis. 33 Only 1 study detected HER2 gene amplification by chromogenic in situ hybridization in feline mammary tumors, 23 whereas no study in veterinary medicine has detected HER2 amplification using the FISH technique.…”

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confidence: 99%

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HER2Amplification Status in Feline Mammary Carcinoma: A Tissue Microarray–Fluorescence In Situ Hydridization–Based Study

Muscatello

Oto²,

Sarli

et al. 2018

Vet Pathol

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Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor overexpressed in a subset of breast cancer due to HER2 gene amplification. HER2 protein is expressed in feline mammary carcinomas, but little is known about its cytogenetic alterations. The aim of this study was to evaluate HER2 gene amplification status and its correlation with HER2 protein expression in feline mammary carcinomas. Feline mammary carcinomas were retrospectively selected and immunohistochemically (IHC) evaluated for HER2 protein expression. All the HER2 IHC-positive (3+) and equivocal (2+) cases and a subset of negative cases (0/1+) were selected for fluorescence in situ hybridization (FISH). Dual-core tissue microarrays were prepared for FISH. IHC and FISH were evaluated according to the 2013 American Society of Clinical Oncology/College of American Pathologists guidelines. The study included 107 feline mammary carcinomas from 88 queens. HER2 protein expression was positive (3+) in 7 cases (6.5%), equivocal (2+) in 48 cases (45%), and negative (0/1+) in 52 cases (48.5%). HER2 status was indeterminate in 8 feline mammary carcinomas (12%), amplified in 3 (4%), equivocal in 4 (6%), and nonamplified in 53 (78%). HER2 gene amplification and protein expression were significantly positively correlated ( R = 0.283; P < .0001). HER2 gene is amplified in a subset of feline mammary carcinomas despite the HER2 positive or equivocal protein expression, but it remains to be determined if the HER2 amplification is a gene alteration that drives mammary tumor carcinogenesis or only a bystander passenger mutation.

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Epidemiology of mammary tumours in bitches under veterinary care in the UK in 2016

et al. 2023

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BackgroundThere is limited information on the epidemiology of canine mammary tumours. This study aimed to estimate the incidence and risk factors for mammary tumours in UK bitches.MethodsA nested case–control study was conducted within VetCompass to estimate the frequency and risk factors for clinically diagnosed mammary tumours during 2016 (VetCompass study). A second case–control study explored further breed associations for cases confirmed histopathologically compared to the VetCompass controls (laboratory study). Multivariable logistic regression was used to evaluate associations between risk factors and mammary tumours.ResultsThe incidence of mammary tumours was 1340.7/100,000 per year (95% confidence interval: 1198.1–1483.3). A total of 222 clinical cases (VetCompass study) and 915 laboratory cases (laboratory study) were compared to 1515 VetCompass controls in the two analyses. In the VetCompass study, Springer and Cocker Spaniels, Boxers, Staffordshire Bull Terriers and Lhasa Apsos had increased odds of developing mammary tumours. Neutering was associated with reduced odds, while odds increased with increasing age and a history of pseudopregnancy. In the laboratory study, increasing age was associated with greater odds of mammary tumours, and the breeds most at risk were similar to those identified in the VetCompass study.LimitationsThe timing of neutering was not consistently available. Comparing laboratory cases to VetCompass controls provided only exploratory evidence for the breed associations identified.ConclusionsThe study provides an update on the frequency of canine mammary tumours.

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Consensus Proposal on Essential Phenotype Markers and Hormone Receptor Assessment in Canine Mammary Tumours

Cited by 23 publications

References 0 publications

Epigenetics in Canine Mammary Tumors: Upregulation of miR-18a and miR-18b Oncogenes Is Associated with Decreased ERS1 Target mRNA Expression and ERα Immunoexpression in Highly Proliferating Carcinomas

Epigenetics in Canine Mammary Tumors: Upregulation of miR-18a and miR-18b Oncogenes Is Associated with Decreased ERS1 Target mRNA Expression and ERα Immunoexpression in Highly Proliferating Carcinomas

HER2Amplification Status in Feline Mammary Carcinoma: A Tissue Microarray–Fluorescence In Situ Hydridization–Based Study

Epidemiology of mammary tumours in bitches under veterinary care in the UK in 2016

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