Reproducibility and Feasibility of Classification and National Guidelines for Histological Diagnosis of Canine Mammary Gland Tumours: A Multi-Institutional Ring Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Papparella S
PROVIDER: S-EPMC9325225 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Canine mammary carcinoma represents a model for the study of human breast cancer, although the prognostic value of various clinical, histological and immunohistochemical parameters has shown contradictory results. A prospective study, through a 4-year follow-up, was performed in 77 patients with mammary carcinoma to analyse the association between histological diagnosis, grade of malignancy, peritumoral and vascular invasion. We have also performed immunohistochemistry for the expression of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and cyclooxygenase-2 (COX-2) that define human biomarkers of disease progression and treatment response. An association between histological diagnosis and clinical stage was observed with a high proportion of complex carcinoma classified as stage I. There was a higher proportion of ER+ /PR+ /HER2- tumours in stage I. In contrast, triple-negative tumours (ER- /PR- /HER2- ) were found mainly in advanced clinical stages and were associated with vascular and peritumoral invasion. The tumours included in group VII (carcinosarcoma/adenosquamous carcinoma/other special types of carcinoma) had a higher expression of COX-2. The univariate analysis showed that those patients with complex carcinoma had the lowest incidence of metastases and the highest probability of survival. In contrast, a high proportion of patients with anaplastic/inflammatory carcinoma developed metastases and showed the lowest probability of survival. In addition, the estimated survival time was shorter for those patients with triple-negative tumours and those with high COX-2 expression. However, in the multivariate analysis, only the peritumoral invasion maintained its prognostic significance. In conclusion, in our study anaplastic/inflammatory carcinomas had the worst prognosis with a high proportion of triple-negative tumours in this category.
| S-EPMC7754150 | biostudies-literature
Project description:IntroductionA vast increase in knowledge of numerous aspects of malignant salivary gland tumours has emerged during the last decade and, for several reasons, this has not been the case in benign epithelial salivary gland tumours. We have performed a literature review to investigate whether an accurate histological diagnosis of the 11 different types of benign epithelial salivary gland tumours is correlated to any differences in their clinical behaviour.MethodsA search was performed for histological classifications, recurrence rates and risks for malignant transformation, treatment modalities, and prognosis of these tumours. The search was performed primarily through PubMed, Google Scholar, and all versions of WHO classifications since 1972, as well as numerous textbooks on salivary gland tumours/head and neck/pathology/oncology. A large number of archival salivary tumours were also reviewed histologically.ResultsPleomorphic adenomas carry a considerable risk (5-15%) for malignant transformation but, albeit to a much lesser degree, so do basal cell adenomas and Warthin tumours, while the other eight types virtually never develop into malignancy. Pleomorphic adenoma has a rather high risk for recurrence while recurrence occurs only occasionally in sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and the membranous type of basal cell adenoma. Papillomas, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (solid, trabecular and tubular subtypes) very rarely, if ever, recur.ConclusionsA correct histopathological diagnosis of these tumours is necessary due to (1) preventing confusion with malignant salivary gland tumours; (2) only one (pleomorphic adenoma) has a considerable risk for malignant transformation, but all four histological types of basal cell adenoma can occasionally develop into malignancy, as does Warthin tumour; (3) sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and Warthin tumour only occasionally recur; while (4) intraductal and inverted papilloma, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (apart from the membranous type) virtually never recur. No biomarker was found to be relevant for predicting recurrence or potential malignant development. Guidelines for appropriate treatment strategies are given.
| S-EPMC6822986 | biostudies-literature
Project description:Spontaneously occurring canine mammary tumours (CMTs) are the most common neoplasms of female unspayed dogs and are of potential importance as models for human breast cancer as well. Mortality rates are thrice higher in dogs as compared to humans with breast cancer, which can partly be attributed to lack of diagnostic techniques for their early detection. Human breast cancer studies reveal role of autoantibodies in early cancer diagnosis and also the usefulness of autoantibody panels in increasing the sensitivity, as well as, specificity of diagnostic assays. Therefore, in this study, we took advantage of high-throughput Luminex technique for developing a multiplex assay to detect autoantibody signatures against 5 canine mammary tumour-associated autoantigens (TAAs). These TAAs were expressed separately as fusion proteins with halo tag at the N-terminus, which allows easy and specific covalent coupling with magnetic microspheres. The multiplex assay, comprising a panel of candidate autoantigens (TPI, PGAM1, MNSOD, CMYC & MUC1) was used for screening circulating autoantibodies in 125 dog sera samples, including 75 mammary tumour sera and 50 healthy dog sera. The area under curve (AUC) of the combined panel of biomarkers is 0.931 (p?<?0.0001), which validates the discriminative potential of the panel in differentiating tumour patients from healthy controls. The assay could be conducted in 3hrs using only 1ul of serum sample and could detect clinical cases of canine mammary tumour with sensitivity and specificity of 78.6% and 90%, respectively. In this study, we report for the first time a multiplexed assay for detection of autoantibodies in canine tumours, utilizing luminex technology and halo-tag coupling strategy. Further to the best of our knowledge, autoantibodies to CMYC and MUC1 have been reported for the first time in canines in this study.
| S-EPMC6202347 | biostudies-literature
Project description:Canine mammary gland tumour (CMTs) are one of the most commonly found tumours in intact female dogs. A previous study on canine mammary glands demonstrated the presence of the transient receptor potential melastatin 7 (TRPM7) ion channels in healthy canine mammary tissues. However, the significance of TRPM7 in CMT is not yet known. TRPM7 is a Ca2+ and Mg2+ permeable cation channel that contains a protein kinase domain. The aim of this study was to determine TRPM7 expression in 57 benign and malignant CMT tissues of dogs using immunohistochemistry (IHC) and evaluate its correlation with clinicopathological features and explore the potential prognostic value of TRPM7 in a prospective survival study. IHC analysis shows that TRPM7 was expressed in the cytoplasm of neoplastic epithelial cells. Moreover, TRPM7 expression was significantly associated with tumour malignancy (P = .027), Ki-67 index (P < .0001) and metastasis (P < .0001). Survival curve analysis indicates that high TRPM7 expression was significantly associated with poor disease-free (P = .035) and overall survival (P = .011) in malignant CMTs. Our results demonstrate that TRPM7 is expressed in CMTs and that its expression is positively correlated with clinicopathological parameters. Thus, TRPM7 was assumed to be a potential prognostic factor for CMTs.
| S-EPMC8453503 | biostudies-literature
Project description:Breast cancer risk from pesticides may be missed if effects on mammary gland are not assessed in toxicology studies required for registration. Using US EPA's registration documents, we identified pesticides that cause mammary tumors or alter development, and evaluated how those findings were considered in risk assessment. Of 28 pesticides that produced mammary tumors, EPA's risk assessment acknowledges those tumors for nine and dismisses the remaining cases. For five pesticides that alter mammary gland development, the implications for lactation and cancer risk are not assessed. Many of the mammary-active pesticides activate pathways related to endocrine disruption: altering steroid synthesis in H295R cells, activating nuclear receptors, or affecting xenobiotic metabolizing enzymes. Clearer guidelines based on breast cancer biology would strengthen assessment of mammary gland effects, including sensitive histology and hormone measures. Potential cancer risks from several common pesticides should be re-evaluated, including: malathion, triclopyr, atrazine, propylene oxide, and 3-iodo-2-propynyl butylcarbamate (IPBC).
| S-EPMC9183204 | biostudies-literature
Project description:BACKGROUND: The limited within-breed genetic heterogeneity and an enrichment of disease-predisposing alleles have made the dog a very suitable model for the identification of genes associated with risk for specific diseases. Canine mammary cancer is an example of such a disease. However, the underlying inherited risk factors for canine mammary tumours (CMTs) are still largely unknown. In this study, 52 single nucleotide polymorphisms (SNPs) in ten human cancer-associated genes were genotyped in two different datasets in order to identify genes/alleles associated with the development of CMTs. The first dataset consisted of English Springer Spaniel (ESS) CMT cases and controls. ESS is a dog breed known to be at increased risk of developing CMTs. In the second dataset, dogs from breeds known to have a high frequency of CMTs were compared to dogs from breeds with a lower occurrence of these tumours. RESULTS: We found significant associations to CMT for SNPs and haplotypes in the estrogen receptor 1 (ESR1) gene in the ESS material (best PBonf?=?0.021). A large number of SNPs, among them several SNPs in ESR1, showed significantly different allele frequencies between the high and low risk breed groups (best PBonf?=?8.8E-32, best PBPerm?=?0.076). CONCLUSIONS: The identification of CMT-associated SNPs in ESR1 in two independent datasets suggests that this gene might be involved in CMT development. These findings also support that CMT may serve as a good model for human breast cancer research.
| S-EPMC3637093 | biostudies-literature
Project description:BackgroundMammary gland tumours are the most frequently diagnosed tumours in the female dogs but just a few studies have analysed their epidemiology. Therefore, we set out to describe the epidemiology of canine mammary cancer in the Canary Archipelago, Spain. We analysed a pathology tumour registry (PTR) and identified 7362 samples obtained from 5240 female dogs resident on the Canary Archipelago during an 18-year period (2003-2020). Using a case-control study design, we compared mammary tumour affected dogs with the Canarian canine population registry in order to elucidate the breed associations for these tumours.ResultsThe frequency of a diagnosis of mammary tumours relative to all tumour diagnoses in female dogs decreased during the study period from 62.7% to 48.9%. Contemporaneously, the proportion of dogs diagnosed with mammary tumours who were also neutered increased from 13.6% to 26.9%. There was a negative correlation (R = -0.84) between these changes. Additional findings were that: the proportion of female dogs diagnosed with multiple tumours increased by 23.5% and that the proportion of malignant tumours 89.2% diagnosed has remained stable through the period. Benign mammary tumours were diagnosed at younger ages (9.2 years old) than carcinomas (9.7 years old) and sarcomas (10.4 years old). Epithelial mammary tumours were diagnosed at younger ages in entire female dogs. Samoyed, Schnauzer, Poodle, German Pinscher and Cocker Spaniel were the breeds with the highest odds-ratios (OR) in comparison with the reference (crossbreeds) while Miniature Pinscher, American Staffordshire Terrier, English Pointer as well as some local breeds such as the Canary Warren Hound and the Majorero had the lowest ORs.ConclusionsThis study provides a description of the changing epidemiology of canine mammary cancer in the Canary Archipelago over the last two decades. We found high rates of CMT with a significant predominance of malignant tumours. Exact risk factors are uncertain, but a combination of environmental, regional socioeconomic affecting human and their pets, and animal management factors are likely to play a part. Specifically, neutering was negatively associated with the proportion of epithelial mammary gland tumours and breeds native to the region were at lower risk of mammary tumours. A deeper analysis of all these factors will facilitate a deeper understanding of the epidemiology of mammary gland tumours in both the canine and the human population.
| S-EPMC9277912 | biostudies-literature
Project description:Early diagnosis of mammary gland tumors is a challenging task in animals, especially in unspayed dogs. Hence, this study investigated the role of microsatellite instability (MSI), MMR gene mRNA transcript levels and SNPs of MMR genes in canine mammary gland tumors (CMT). A total of 77 microsatellite (MS) markers in 23 primary CMT were selected from four breeds of dogs. The results revealed that 11 out of 77 MS markers were unstable and showed MSI in all the tumors (at least at one locus), while the other markers were stable. Compared to the other markers, the ABC9TETRA, MEPIA, 9A5, SCNA11 and FJL25 markers showed higher frequencies of instability. All CMT demonstrated MSI, with eight tumors presenting MSI-H. The RT-qPCR results revealed significant upregulation of the mRNA levels of cMSH3, cMLH1, and cPMSI, but downregulation of cMSH2 compared to the levels in the control group. Moreover, single nucleotide polymorphisms (SNPs) were observed in the cMSH2 gene in four exons, i.e., 2, 6, 15, and 16. In conclusion, MSI, overexpression of MMR genes and SNPs in the MMR gene are associated with CMT and could be served as diagnostic biomarkers for CMT in the future.
| S-EPMC7169452 | biostudies-literature
Project description:Studies of naturally occurring cancers in dogs, which share many genetic and environmental factors with humans, provide valuable information as a comparative model for studying the mechanisms of human cancer pathogenesis. While individual and small-scale studies of canine cancers are underway, more generalized multi-omics studies have not been attempted due to the lack of large-scale and well-controlled genomic data. Here, we produced reliable whole-exome and whole-transcriptome sequencing data of 197 canine mammary cancers and their matched controls, annotated with rich clinical and biological features. Our dataset provides useful reference points for comparative analysis with human cancers and for developing novel diagnostic and therapeutic technologies for cancers in pet dogs.
| S-EPMC6694171 | biostudies-literature
Project description:Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in human breast cancer. Since there is little information about SSTR2 in canine mammary gland tumor (MGT), we clarified its distribution and expression level in normal mammary gland, benign MGT and malignant MGT. SSTR2 expression determined by immunohistochemical staining was observed in the cytoplasm of luminal epithelial cells. The intensity was negatively correlated with malignancy: normal tissues and some of the benign tumors had the highest levels, while the malignant tumors had little or no SSTR2 expression. As for the Western blotting, SSTR2 protein level in benign tumors was significantly lower than the normal mammary gland. On the other hand, SSTR2 protein levels in two of three malignant tumors were higher than the other groups. These results suggest that SSTR2 expression alters according to the malignancy of canine MGT.
| S-EPMC4638304 | biostudies-literature