Search Results (58)

Mammary tumors are the most common neoplasms diagnosed in female dogs and have been considered excellent models for studying human breast cancer. Establishing cell lines from primary cultures of canine mammary tumors provides an in vitro model to better understand the disease and develop new treatments. This study aimed to establish and characterize canine mammary tumor cell lines. Ten cell cultures were generated from tumor tissue obtained from affected dogs, including seven from primary mammary tumors and three from metastatic sites. Characterization included molecular marker expression (ER, PR, HER2, cytokeratin 5/6 (CK5/6), vimentin, and the marker of cell proliferation Ki67) and in vitro tumorigenic capacity assessment. Additionally, the susceptibility of five cell lines to DOX, 5-FU, paclitaxel, colchicine, and carboplatin was evaluated using the MTT assay. ICC analysis revealed negative expression of hormonal receptors (ER and PR) in five cell lines, while only one cell line was positive for both. Six cell lines were HER2-negative and positive for vimentin. Five cell lines exhibited in vitro tumorigenic capacity, forming colonies in soft agar. DOX showed the highest growth-inhibitory effect (DOX > Paclitaxel > Colchicine > 5-FU > Carboplatin). Two cell lines had a minimal concentration for 50% inhibition in vitro (IC₅₀) < 0.63 µM and 4.37 ± 0.40 µM for DOX, while one was sensitive to colchicine and paclitaxel (IC₅₀ 0.19 µM and 0.04 µM, respectively). All tested cell lines were resistant to carboplatin and 5-FU. These cell lines provide a valuable model for studying breast cancer in humans and dogs and evaluating new potential therapeutic strategies. Full article

Mammary tumors are the most common neoplasms in female dogs, with mastectomy being the primary treatment. The impact of mastectomy type on survival remains unclear. This study evaluated the effect of different surgical techniques on the survival of female dogs with mammary carcinomas. A total of 307 dogs with 734 mammary tumors were analyzed. Ages ranged from 1 to 17 years, with mixed breeds comprising 48.9%. Most tumors (92.9%) were malignant, predominantly carcinoma in a mixed tumor (30.2%). Unilateral mastectomy was the most common technique (65.8%). Lumpectomy showed the shortest mean survival (179 days) and was associated with a 4.9-fold increased risk of death (p = 0.009). There was no significant association between surgical technique and overall survival or recurrence of mammary carcinoma (p = 0.2). This study relied on owner-reported data for survival and tumor recurrence. Lumpectomy appears to be associated with shorter survival times in female dogs with mammary carcinoma. Therefore, it may be advisable to reconsider this technique as a primary treatment option. Full article

In cancer cases, any imbalance between Reactive Oxygen Species (ROS) production and host antioxidant capacity (oxidative stress), during the immediate post-operative period, is involved in cancer cell dissemination (micro-metastases). Surgical trauma is considered the main cause for ROS production during that period. Increased oxidative stress has been found in dogs with mammary neoplasms. Our objective was to investigate the blood oxidant/antioxidant profile in bitches with mammary cancer, during the peri-operative period, hypothesizing that oxidative stress would be further increased after mastectomy. Twelve bitches with mammary cancer and no distant metastases, with a comparable extent of surgical wound and receiving the same anesthetic protocol, were included. Their serum oxidant/antioxidant profile was evaluated chromatometrically using the d-ROMs (Reactive Oxygen Metabolite-derived compounds) and the BAP (biological antioxidant potential) tests, on the 1st day (before/after surgery), and on the 2nd, 3rd and 10th days post-operatively. The ratio of d-ROMs and BAP values (oxidative stress index; OSI) was also calculated. Statistically significant differences (increases) were found only in d-ROMS on the second and third post-operative day compared to the first day (before surgery) of measurement (p = 0.007 and p = 0.002, respectively). Our findings indicate a post-surgical overproduction of ROS and therefore an oxidative stress increase potentially affecting patient outcome. Full article

Canine mammary tumors (CMTs) constitute one of the most prevalent malignancies in female canines, whereas the functional involvement of gonadotropin receptors—luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR)—in these neoplasms remains uncharacterized. This study investigated LHR and FSHR expression in 79 CMTs and 14 normal mammary tissues collected from 59 female dogs (ethical approval AW82903202-2-3), using immunohistochemistry (IHC) and quantitative real-time PCR, specifically examining their association with tumor malignancy and spay status. Relative to normal mammary tissue, CMTs exhibited statistically significant downregulation of both LHR and FSHR transcripts and corresponding proteins (p < 0.01), with expression progressively decreasing as tumor malignancy increased, and with grade 3 tumors showing almost undetectable levels. Notably, spayed dogs displayed higher LHR levels in tumors (p < 0.05), whereas intact dogs showed higher FSHR levels than spayed dogs. These findings suggest that the expression of LHR and FSHR in CMTs may correlate with tumor malignancy and be influenced by the spay status. Our findings provide the first evidence of gonadotropin receptor dysregulation in CMTs, offering novel insights into their molecular mechanisms and potential applications in hormone-related diagnostic or therapeutic strategies. Full article

Mixed-type carcinoma (MTC) accounts for 44% of mammary neoplasms in bitches and poses challenges in histological grading due to the heterogeneity of invasive areas. The present study aimed to measure and characterize invasive areas in the stroma of MTC and investigate the association of those parameters with lymph node status and survival. Forty cases were analyzed and divided into two groups: with metastasis and without metastasis. The size, perimeter, length, and number of invasive carcinomatous areas were measured. Cases with metastasis showed a higher number of foci (p = 0.003) and larger invasive areas (p = 0.006) compared to cases without metastasis. Bitches with invasive areas larger than 2 mm² had shorter survival times. No association was found between the perimeter or length of invasive areas, the expression of Ki67, ER, PR, COX-2, HER-2, and the immunophenotype. Thus, the number and size of invasive areas are associated with regional lymph node status, suggesting histomorphometry may serve as a valuable tool for evaluating the biological behavior of mixed-type carcinoma. Full article

Feline mammary carcinoma (FMC) is an aggressive neoplasm with a poor prognosis. Clinical staging is crucial for risk assessment, yet the current WHO system lacks granularity, particularly in Stage III. Aligning this system with human breast cancer staging has the potential to improve prognostic accuracy. Additionally, prognostic factors such as tumor size, ulceration, lymph node metastasis, and lymphovascular invasion require further evaluation. This study retrospectively analyzed 75 female cats with FMC to assess the prognostic impact of clinicopathological factors and evaluate a novel staging system (new staging) adapted from the AJCC Cancer Staging Manual. Survival analyses included disease-free interval (DFI), and overall survival (OS). Tumor size >3 cm (p < 0.001), ulceration (p = 0.010), lymphovascular invasion (p < 0.001), lymph node metastasis (p < 0.001), WHO and new staging (p < 0.001) were significantly associated with shorter survival. The new staging refined Stage III into III_A (T₃N₀M₀), III_B (T₄N₀M₀), and III_C (AnyTN₁M₀), improved prognostic differentiation. Stage III_C cases had the worst survival (p < 0.001). Multivariate survival analysis identified lymphovascular invasion (HR = 2.834, 95% CI: 1.546–5.195, p = 0.001), histological Grade II (HR = 5.013, 95% CI: 1.122–22.397, p = 0.035) and III (HR = 9.894, 95% CI: 2.195–44.594, p = 0.003) and skin ulceration (HR = 2.462, 95% CI: 1.256–4.825, p = 0.009). These findings support the prognostic relevance of key clinicopathological factors in FMC and highlight the advantages of a refined TNM-based staging system, which may enhance risk stratification and therapeutic decision-making in veterinary oncology. Full article

In veterinary medicine, mammary tumors are the most common neoplasms in female dogs and the third most frequent in cats, representing a significant challenge. Efforts have been directed toward adopting standardized diagnostic criteria to better understand tumor behavior and progression in these species. Meanwhile, the use of animal models has substantially advanced the understanding of comparative mammary carcinogenesis. These models provide critical insights into factors responsible for the disease in humans, with the expectation that such factors can be identified and controlled. In this context, this review presents a work based mainly on articles published by a research group specializing in mammary pathology (Laboratory of Comparative Pathology–Department of General Pathology–ICB/UFMG) and its collaborators, complementing their results with literature findings. The publications were categorized into animal research, experimental research, and human research. These studies addressed topics such as diagnosis, prognostic and predictive factors, tumor microenvironment, inflammation associated with tumors, treatment approaches, and factors influencing tumor growth. The conceptual network analysis underscores the importance of in vivo breast cancer models, both experimental and spontaneous, for understanding tumor progression mechanisms and therapeutic responses, offering valuable contributions to veterinary and human oncology. Full article

Mammary neoplasms in dogs are a common clinical concern, especially in middle-aged and older intact females. These tumors share similarities with human breast cancer in terms of histology, disease progression, and risk factors, making dogs a relevant model for breast cancer research. The search for biomarkers in canine mammary tumors is essential to understand tumor progression and identify potential therapeutic targets. This study investigated the expression of two potential biomarkers—Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 (ITIH2) and Enolase 1 (ENO1)—in the mammary glands of healthy and tumor-bearing dogs using immunohistochemistry. Both proteins were identified in previous proteomic analyses of extracellular vesicles derived from the plasma of healthy and tumor-bearing dogs. A total of fifty-one canine mammary tissue samples were analyzed and categorized into three groups: (i) the control group, composed of five samples of normal mammary tissue without neoplasia; (ii) benign tumors, composed of nineteen samples of benign mixed tumors; and (iii) malignant tumors, which included six carcinomas in grade 1 mixed tumors, five carcinomas in grade 2 mixed tumors, thirteen solid carcinomas of grade 3, one papillary carcinoma, and two tubular carcinomas. Regarding the intensity of staining, quantified by histoscore, there were no significant differences in the comparison between the groups; for ITIH2, the p-value was 0.33, and for ENO1, the p-value was 0.57. Regarding the predictive potential of their respective ROC curves, the proteins demonstrated low predictive power in canine mammary tumors. These findings indicate that neither ITIH2 nor ENO1 demonstrated strong prognostic value in this setting, as demonstrated by their moderate AUC values, wide confidence intervals, and lack of statistical significance. However, this study found distinct tissue localization patterns for ITIH2 and subcellular localization for ENO1. As an additional way to examine possible associations of these proteins with epithelial–mesenchymal transition, the ZEB1 antibody was tested by both single and double immunohistochemistry, demonstrating a tendency to be more intensely expressed in the malignant group and tending to be associated with ENO1 in canine mammary tumors. Full article

In canine mammary neoplasms, greater inflammation is associated with higher histological grade, lymphatic invasion, and metastases. This retrospective study assessed the density of peri- and intratumoral tumor-infiltrating lymphocytes (TILs), tumor-associated neutrophils (TANs), and CD3⁺ and CD79⁺ lymphocytes in canine mammary neoplasms with a solid arrangement, and associated such data with histological types, immunophenotype, prognostic factors, cyclooxygenase-2 (Cox-2) expression and overall and cancer-specific survival. Sixty-one neoplasms with a solid arrangement were classified as malignant myoepitheliomas (6/9.8%), solid papillary carcinomas (8/13.1%), carcinomas with a solid pattern (9/14.8%), basaloid carcinomas (BC) (19/31.1%), and malignant adenomyoepitheliomas (19/31.1%). Intra- and peritumoral TILs, TANs, and TCD3⁺ and BCD79⁺ lymphocytes were counted, and based on the resulting median, the neoplasms were divided into low or high cell infiltration. BCs had the lowest density of intratumoral TILs (p = 0.02), and luminal B neoplasms showed a significantly higher density of intratumoral TCD3⁺ than luminal A cases. Neoplasms with a higher density of peritumoral CD3⁺ and CD79⁺ had significantly greater proliferative activity. High infiltration of intratumoral BCD79⁺ lymphocytes was related to nodal metastasis (p = 0.03). Intratumoral TILs and TCD3⁺ were associated with shorter survival time. Therefore, intratumoral lymphocyte infiltration is possibly an important feature in the progression of cancer and influences the survival in bitches with solid arrangement neoplasms. Full article

Background: Somatostatin receptors (SSTRs) are expressed in most neuroendocrine neoplasms, particularly in gastroenteropancreatic neuroendocrine tumours, and have been utilised as diagnostic markers and therapeutic targets. The radioiodinated somatostatin analogue 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid- Tyr3-octreotate (DOTATATE) has been employed for SSTR targeting for either diagnostic or therapeutic purposes depending on the labelling with ⁶⁸Gallium or ¹⁷⁷Lutetium, respectively. SSTR expression is reported in a subset of breast adenocarcinoma and breast neuroendocrine carcinomas; however, minimal knowledge exists regarding their expression in fibroepithelial (biphasic) breast lesions such as fibroadenoma and phyllodes tumours. Aggressive ends of the spectrum, i.e., “cystosarcoma phyllodes”, may present a management challenge with recurrences and metastases, and SSTRs could be a promising therapeutic target for these types of tumours. Methods: Gene and protein expressions of SSTRs in primary human fibroepithelial lesions of the breast are investigated using RT-PCR and immunoblotting. Localisation of the SSTR-positive cells was determined with immunohistochemistry and immunofluorescence. Results and Conclusions: Both fibroadenoma and phyllodes tumours express SSTRs. Immunohistochemical analyses suggested that this expression is in the stromal, not epithelial, component by demonstrating that SSTR stained in the areas overlapping with α-smooth muscle actin-positive myoepithelial cells around blood vessels and capillary structures. This study is the first in the literature to demonstrate SSTR positivity in mammary fibroepithelial neoplasms. Once validated, these findings may also have significant implications for managing the treatment of these tumours. Full article

A seven-year-old spayed female dog presented with multiple, small oval-shaped masses on the abdominal skin. The excised tissue was submitted for histopathological evaluation. Routine histology revealed basaloid nodules with stippled chromatin and pleomorphic nuclei. Morphologically, the tumor resembled a solid papillary carcinoma of the breast or an endocrine mucin-producing sweat gland carcinoma (EMPSGC). EMPSGC is a rare neuroendocrine-differentiated neoplasm. This study aimed to compare different immunohistochemical markers for distinguishing between canine sweat gland carcinoma (SGC) and mammary gland carcinoma (MGC). CK19 and Sox9 were useful in identifying SGC. Additionally, the tumor was positive for CK5, AE1/AE3+CK8/18, p63, vimentin, E-cadherin, and synaptophysin, while estrogen receptor staining was negative. The final diagnosis of canine EMPSGC was based on the tumor’s morphological and neuroendocrine immunohistopathological features. Our report provides the first detailed description of a canine EMPSGC, an exceedingly rare tumor in dogs. Full article

Mast cell tumors (MCTs) are common skin neoplasms in dogs. Prognostic indicators include histologic grade, clinical stage, high Ki-67 index, elevated argyrophilic nucleolus organizer regions (AgNOR) index, c-kit mutations, and recurrence after surgery. Blood serum redox status has been shown to correlate with prognostic factors in canine lymphoma and mammary tumors. This study aimed to assess the correlation between established prognostic factors and serum redox status and lipid metabolism analytes in dogs with MCTs. Dogs with cutaneous (n = 33) or subcutaneous (n = 6) MCTs, without comorbidities, were studied. Staging was evaluated based on cytology of regional lymph nodes and ultrasound-guided liver and spleen aspiration cytology. Histologic grading and immunohistochemical staining for Ki-67 and KIT patterns were performed on excised tumor specimens. Dogs were categorized by Patnaik grading (1–3), Kiupel grading (low/high), metastatic status, Ki-67 positive nuclei per cm² (>23 or ≤23), and KIT pattern (I, II–III). Paraoxonase-1, Butyrylcholinesterase, Cupric Reducing Antioxidant Capacity (CUPRAC), Diacron Reactive Oxygen Metabolites (d-ROMs), and oxy-adsorbent levels were measured before any therapeutic intervention. ANOVA and independent t-tests were used to detect differences in the mean values among groups. Paraoxonase-1 activity was significantly lower in Patnaik grade 3 (p = 0.003) and Kiupel high-grade (p = 0.022) MCTs. No significant differences were found in CUPRAC, d-ROMs, or oxy-adsorbent levels across different prognostic groups. This study found a significant correlation between histologic grading and Paraoxonase-1 activity, suggesting a potential role of Paraoxonase-1 as a prognostic biomarker in canine MCTs. Full article

Necrosis is a common finding in human and animal neoplasms. The percentage of tumor necrosis is included in tumor grading schemes in veterinary oncology; however, evaluation methods are often overlooked. Different studies have assessed the prognostic value of tumor necrosis in feline mammary tumors with contradictory results, which could be related to methodologic variability. In this study, a comprehensive evaluation of tumor necrosis in feline mammary tumors (FMTs) was conducted, by applying a semi-quantitative and a quantitative methodology for assessing necrosis. The interobserver agreement, the relationship with clinicopathological characteristics and the prognostic value of necrosis were analyzed in 154 FMT cases. Although subjectivity in the assessment of necrosis existed, an almost perfect agreement (weighted quadratic k = 0.851) between two observers was obtained. Furthermore, there was a significant positive correlation between the semi-quantitative and quantitative methods. Necrosis was more common and more extensive in malignant tumors than in their benign counterparts. Despite the non-significant results in the survival analysis, extensive necrosis was significantly associated with aggressive clinicopathological features, such as higher histological grade, high mitotic count and lymphovascular invasion. Our results support the potential relevance of necrosis in FMT. Full article

Most lesions found in the mammary glands of cats are malignant, with aggressive behavior and unfavorable prognosis. Studies on the epidemiologic and clinicopathological characteristics of mammary lesions in cats are scarce. The present study aimed to evaluate those characteristics and to correlate them with survival in cats. Mammary specimens were selected from 418 domestic cats that underwent surgical removal with or without lymphadenectomy. The cats and mammary lesions were evaluated for epidemiologic, clinical, and pathologic characteristics. Cats with malignant neoplasms were older than cats with benign neoplasms and non-neoplastic lesions; 858 lesions were identified, including sporotrichosis, basaloid carcinoma, and benign phyllodes, described for the first time in cats. Tubulopapillary and cribriform carcinomas were the most common malignant tumors found and were very similar in characteristics such as marked anisocytosis/anisokaryosis, high mitotic count (score 3) (p < 0.001), and presence of necrosis (p = 0.005). The association between advanced age and malignancy, as well as the description of new lesions, emphasizes the importance of population studies in cats to understand the behavior of the disease and to draw attention to diagnoses that should be considered in routine care. Full article

Mammary tumors are one of the most common neoplasms in female dogs, and cytology represents a non-invasive diagnostic method. The protozoal pathogen Leishmania spp. was previously demonstrated in canine mammary glands. An eight-year-old, female-spayed Doberman was imported from Crete, Greece, three years before the first presentation. The dog was presented due to a mammary tumor two years after adoption. The clinical examination revealed fever and weight loss. Smears of the mammary secretion were investigated cytologically. Multiple atypical epithelial cells with moderate to marked criteria of malignancy were detected. Furthermore, amastigotes were visible intra- and extracellularly. The diagnosis of L. infantum infection was based on a positive PCR out of the cytological smear, and a positive serology. Mammary carcinoma and granulomatous inflammation with amastigotes were confirmed by histopathology. We aimed to provide a complete report of cytological, histopathological, hematological, and biochemistry findings in a dog with L. infantum in the mammary glands with focus on trans-mammary pathogen transmission as a potential alternative way of spreading Leishmania infections. Canine leishmaniasis should be a potential differential diagnosis in dogs with lesions and/or inflammation in the mammary glands and a history of presence in areas endemic for L. infantum, especially the Mediterranean in Europe. Full article