Veterinary Sciences

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12 pages, 1031 KiB

Open AccessArticle

Ki67 Index in Patnaik Grade 2/Kiupel Low-Grade Canine Cutaneous Mast Cell Tumors with Early Lymph Node Metastasis: A Descriptive Study

by Marzia Cino, Elisa Maria Gariboldi, Damiano Stefanello, Kevin Pascal Spindler, Erica Ilaria Ferraris, Emanuela Maria Morello, Luca Bertola, Lorella Maniscalco and Marina Martano

Vet. Sci. 2023, 10(7), 436; https://doi.org/10.3390/vetsci10070436 - 5 Jul 2023

Cited by 3 | Viewed by 3772

Abstract

Several studies evaluating Ki67 in canine cutaneous mast cell tumors (cMCTs) have reported its prognostic value when tumors of all histological grades are included. This study aims to evaluate whether the Ki67 index has a predictive value in a homogeneous cohort of G2/LG [...] Read more.

Several studies evaluating Ki67 in canine cutaneous mast cell tumors (cMCTs) have reported its prognostic value when tumors of all histological grades are included. This study aims to evaluate whether the Ki67 index has a predictive value in a homogeneous cohort of G2/LG cMCTs with HN2 lymph nodes (LNs) and to describe the clinical outcome. The second goal was to explore the correlation between the Ki67 index and MC. The medical databases of three institutions were retrospectively searched for dogs undergoing surgical treatment for cMCT and LN extirpation, with a histological diagnosis of G2/LG with HN2 LNs. Information about histological margins, MC, Ki67 index, local recurrence, nodal relapse, distant metastasis, de novo cMCT occurrence and date and cause of death were included. A total of 39 cases were identified. None of these developed local and nodal relapse or metastatic distant disease. Median MC was 1 (0–2). Median Ki67 index was 3.5 (0.7–14.3). Ki67 and MC were not significantly correlated. At the end of the study, 32 (82%) dogs were alive, 7 (18%) dogs were dead from unrelated causes and 4 (10.2%) dogs were lost to follow-up. The median ST was not reached, and the mean was 893 days (104–2241 days). Considering the strict inclusion criteria, dogs affected by G2/LG with HN2 LNs treated with surgery alone may have a good oncologic outcome; the Ki67 index does not have prognostic impact. Full article

(This article belongs to the Special Issue Comparative Pathology of Cancers in Animals)

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8 pages, 1153 KiB

Open AccessArticle

Investigating a Prognostic Factor for Canine Hepatocellular Carcinoma: Analysis of Different Histological Grading Systems and the Role of PIVKA-II

by Lorella Maniscalco, Katia Varello, Emanuela Morello, Vittoria Montemurro, Matteo Olimpo, Davide Giacobino, Giuseppina Abbamonte, Cecilia Gola, Selina Iussich and Elena Bozzetta

Vet. Sci. 2022, 9(12), 689; https://doi.org/10.3390/vetsci9120689 - 10 Dec 2022

Cited by 1 | Viewed by 2117

Abstract

Background: Hepatocellular carcinoma (HCC) in dogs is uncommon and often associated with a good prognosis, although some cases prove to be aggressive. In human oncology HCC is often very aggressive and diagnostic methods and prognostic factors are widely used to predict its biological [...] Read more.

Background: Hepatocellular carcinoma (HCC) in dogs is uncommon and often associated with a good prognosis, although some cases prove to be aggressive. In human oncology HCC is often very aggressive and diagnostic methods and prognostic factors are widely used to predict its biological behaviour. These include the expression of PIVKA-II. Methods: in order to identify a prognostic factor for canine HCC, we applied different methods of histological grading and investigated PIVKA-II expression in 22 HCC of dogs treated surgically and followed clinically for at least 2 years. Results: Nineteen patients analysed have passed the observation period without tumour recurrence, while 3 died following the development of metastases. PIVKA-II was positive in 15/22 cases without correlation with prognosis or tumoural grading even if a trend of PIVKA-II negativity in low WHO grades as well as increased number of PIVKA-II positive cases in higher WHO grades weres observed. Conclusions: This work showed that, PIVKA-II cannot be considered either as a marker of malignancy or as a prognostic marker for canine HCC. The poor prognosis depends usually on the clinical presentation. Thus prognostic parameters in canine HCC able to predict its aggressive behaviour through histological examination are still missing. The most promising method, limited to our study, seems to be the WHO histological grading. Full article

(This article belongs to the Special Issue Comparative Pathology of Cancers in Animals)

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10 pages, 3483 KiB

Open AccessArticle

Does TLS Exist in Canine Mammary Gland Tumours? Preliminary Results in Simple Carcinomas

by Giada Giambrone, Stefania Di Giorgio, Cecilia Vullo, Gabriele Marino, Roberto Puleio, Francesca Mariotti, Giuseppe Mazzullo and Alessandra Sfacteria

Vet. Sci. 2022, 9(11), 628; https://doi.org/10.3390/vetsci9110628 - 11 Nov 2022

Cited by 7 | Viewed by 2554

Abstract

Neoplastic progression is influenced by the expression of tumour antigens that activate an anti-tumour immune response. Human medical studies show that this body defence is carried out in secondary lymphoid organs (SLOs) but also directly in the tumour through organized cellular aggregates that [...] Read more.

Neoplastic progression is influenced by the expression of tumour antigens that activate an anti-tumour immune response. Human medical studies show that this body defence is carried out in secondary lymphoid organs (SLOs) but also directly in the tumour through organized cellular aggregates that are called tertiary lymphoid structures (TLSs). However, their occurrence has different meanings in different tumour types. For example, the presence of TLSs in breast cancer is associated with the most aggressive subtypes. This paper aimed to study TLSs in canine mammary simple carcinomas. A morphological assessment of the inflammatory infiltrate was performed on H&E sections of fifty cases. Immunohistochemistry was then carried out to typify the inflammatory cells in the tumour microenvironment. Results showed that, sometimes, inflammatory infiltrates were organized in follicles close to high-grade carcinomas, simulating a lymphoid organization, as in breast cancer. Therefore, we can assume that even in canine mammary tumours, TLSs exist and they are entities to consider due to their presence in the most aggressive histotypes or tumours with a high degree of malignancy. Full article

(This article belongs to the Special Issue Comparative Pathology of Cancers in Animals)

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14 pages, 2293 KiB

Open AccessArticle

Molecular Characterization of CF33 Canine Cell Line and Evaluation of Its Ability to Respond against Infective Stressors in Sight of Anticancer Approaches

by Elisabetta Razzuoli, Chiara Grazia De Ciucis, Barbara Chirullo, Katia Varello, Roberto Zoccola, Lisa Guardone, Paola Petrucci, Danja Rubini, Elena Bozzetta, Maria Goria, Floriana Fruscione and Paola Modesto

Vet. Sci. 2022, 9(10), 543; https://doi.org/10.3390/vetsci9100543 - 2 Oct 2022

Cited by 3 | Viewed by 2650

Abstract

Spontaneous mammary tumors are the most frequent neoplasms in bitches and show similarities with human breast cancer in risk factors, clinical course, and histopathology. The poor prognosis of some cancer subtypes, both in human and dog, demands more effective therapeutic approaches. A possible [...] Read more.

Spontaneous mammary tumors are the most frequent neoplasms in bitches and show similarities with human breast cancer in risk factors, clinical course, and histopathology. The poor prognosis of some cancer subtypes, both in human and dog, demands more effective therapeutic approaches. A possible strategy is the new anticancer therapy based on immune response modulation through bacteria or their derivatives on canine mammary carcinoma cell lines. The aim of the present study was to analyze the CF33 cell line in terms of basal expression of immune innate genes, CXCR4 expression, and interaction with infectious stressors. Our results highlight that CF33 maintains gene expression parameters typical of mammary cancer, and provides the basal gene expression of CF33, which is characterized by overexpression of CXCR4, CD44, RAD51, LY96, and a non-continuous expression of TP53 and PTEN. No mutations appeared in the CXCR4 gene until the 58th passage; this may represent important information for studying the CXCR4 pathway as a therapeutic target. Moreover, the CF33 cell line was shown to be able to interact with Salmonella Typhimurium (ST) (an infective stressor), indicating that these cells could be used as an in vitro model for developing innovative therapeutic approaches involving bacteria. Full article

(This article belongs to the Special Issue Comparative Pathology of Cancers in Animals)

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15 pages, 65315 KiB

Open AccessArticle

Strain and Shear-Wave Elastography and Their Relationship to Histopathological Features of Canine Mammary Nodular Lesions

by Marcella Massimini, Alessia Gloria, Mariarita Romanucci, Leonardo Della Salda, Lucia Di Francesco and Alberto Contri

Vet. Sci. 2022, 9(9), 506; https://doi.org/10.3390/vetsci9090506 - 15 Sep 2022

Cited by 6 | Viewed by 3000

Abstract

Mammary gland tumours have a significant impact on the health of dogs, requiring diagnostic tools to support clinicians to develop appropriate therapeutic strategies. Sonoelastography is an emerging technology that is able to define the stiffness of the tissue and has promising applications in [...] Read more.

Mammary gland tumours have a significant impact on the health of dogs, requiring diagnostic tools to support clinicians to develop appropriate therapeutic strategies. Sonoelastography is an emerging technology that is able to define the stiffness of the tissue and has promising applications in the evaluation of mammary gland lesions. In the present study, strain elastography (STE) and shear-wave (SWE) elastography were compared in 38 mammary nodular lesions for their ability to define the histopathological features of canine mammary lesions. Among the techniques, SWE showed better repeatability (intraclass correlation coefficient: 0.876), whereas STE was found to be only acceptable (intraclass correlation coefficient: 0.456). Mammary nodular lesions showed a wide range of tissue stiffening with a similar mean value for STE and SWE in benign (4 ± 0.3 and 115.4 ± 12.6 kPa, respectively) and malignant lesions (3.8 ± 0.1 and 115.5 ± 4.5 kPa, respectively). A significant correlation was found between lesion fibrosis and STE (STE-I: r = 0.513, p < 0.001; STE-R: r = 0.591, p < 0.001) or SWE-S (r = 0.769; p < 0.001). In conclusion, SWE was reliable and correlated with fibrosis and was similar for both benign and malignant lesions, suggesting that other collateral diagnostic techniques should be considered in conjunction with SWE to characterize mammary nodular lesions in dogs. Full article

(This article belongs to the Special Issue Comparative Pathology of Cancers in Animals)

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13 pages, 2698 KiB

Open AccessArticle

Implication of Netrin-1 Gain of Expression in Canine Nodal Lymphoma

by Antonin Tortereau, Nadège Milhau, Elodie Rhumy, Marie Castets, Frédérique Ponce, Patrick Mehlen and Thierry Marchal

Vet. Sci. 2022, 9(9), 494; https://doi.org/10.3390/vetsci9090494 - 10 Sep 2022

Viewed by 2330

Abstract

Netrin-1 is a member of the laminin superfamily, and is known to interact with specific receptors, called dependence receptors. While upon netrin-1 binding these receptors initiate positive signaling, in absence of netrin-1, these receptors trigger apoptosis. Tumor cells can avoid apoptosis by inactivating [...] Read more.

Netrin-1 is a member of the laminin superfamily, and is known to interact with specific receptors, called dependence receptors. While upon netrin-1 binding these receptors initiate positive signaling, in absence of netrin-1, these receptors trigger apoptosis. Tumor cells can avoid apoptosis by inactivating these receptors or by gaining ligand expression. The aim of the present study was to investigate the expression of netrin-1, the ligand of dependence receptors, in canine healthy lymph nodes (LN), and in lymphomas and to evaluate efficiency of a netrin-1 interfering compound in cell cultures from canine lymphoma. Thirty-two control LN and 169 lymphomas were analyzed through immunohistochemistry. Netrin-1 was expressed in the nucleoli of lymphoid and non-lymphoid cells in controls. Acquisition of a cytoplasmic expression was present in B-cell lymphomas (23.1 % in low-grade and 50.6% in high-grade) and T-cell lymphomas (50.0 % in low-grade and 78.8 % in high-grade), with a significant difference between the high- and low-grade in B-cell lymphomas. Through flow cytometry, we showed a significant increase in netrin-1 expression in either high-grade B-cell and T-cell lymphomas (19 and 5, respectively) compared with healthy LN (5), likewise an RT-qPCR analysis demonstrated a significant increase in netrin-1 expression level in 14 samples of lymphomas compared with eight samples of healthy LN. A T-cell aggressive canine lymphoma cell line and four primary canine nodal lymphomas cell cultures were treated with a netrin-1 interfering antibody. Apoptosis by measuring caspase 3 activity was significantly increased in the cell line and viability was decreased in three of the four primary cell cultures. Together, these data suggest that netrin-1 expression is increased in lymphoma, and more specifically in high-grade lymphomas, and that netrin-1 can act as a survival factor for the neoplastic cells, and so be a therapeutic target. Full article

(This article belongs to the Special Issue Comparative Pathology of Cancers in Animals)

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9 pages, 783 KiB

Open AccessArticle

Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids

by Giorgia Tura, Barbara Brunetti, Elena Brigandì, Riccardo Rinnovati, Giuseppe Sarli, Giancarlo Avallone, Luisa Vera Muscatello, Roberto Marcello La Ragione, Andy E. Durham and Barbara Bacci

Vet. Sci. 2022, 9(9), 474; https://doi.org/10.3390/vetsci9090474 - 1 Sep 2022

Cited by 3 | Viewed by 2005

Abstract

Sarcoids are among the most common tumors diagnosed in equids; their association with bovine papillomaviruses (BPV) infection has been widely reported, but the mechanism of carcinogenesis has not been fully elucidated. To verify whether BPV infection causes dysregulation of the pRb-Cyclin D1-p16^CDKN2A [...] Read more.

Sarcoids are among the most common tumors diagnosed in equids; their association with bovine papillomaviruses (BPV) infection has been widely reported, but the mechanism of carcinogenesis has not been fully elucidated. To verify whether BPV infection causes dysregulation of the pRb-Cyclin D1-p16^CDKN2A-p53 pathway as reported for human papillomavirus (HPV), the study employed immunohistochemistry to test 55 equine sarcoid biopsies for the expression of pRb, Cyclin D1, and p53 cell cycle regulatory proteins and to evaluate the proliferative rate through Ki67. High Cyclin D1 and pRb expression were observed in 51% and 80% of cases, respectively, while low expression was observed in 49% and 20% of cases, respectively. Significantly higher Ki67 proliferation indexes were observed in fibroblastic, nodular, and mixed sarcoids compared to the occult and verrucous. High proliferation was significantly associated with high Cyclin D1 expression. In contrast with previous studies, p53 positivity was not observed in the cases examined in this study. Moreover, follow-up analysis revealed that fibroblastic, mixed sarcoids were associated with significantly higher local recurrence rates while the verrucous subtype was associated with higher rates of new sarcoid development at distant sites. Full article

(This article belongs to the Special Issue Comparative Pathology of Cancers in Animals)

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8 pages, 1077 KiB

Open AccessArticle

Auricular Non-Epithelial Tumors with Solar Elastosis in Cats: A Possible UV-Induced Pathogenesis

by Francesca Millanta, Francesca Parisi, Alessandro Poli, Virginia Sorelli and Francesca Abramo

Vet. Sci. 2022, 9(2), 34; https://doi.org/10.3390/vetsci9020034 - 18 Jan 2022

Cited by 4 | Viewed by 3504

Abstract

The photoinduced etiopathology of actinic keratosis and squamous cell carcinoma in feline species is well known. This etiology has also been reported for non-epithelial cutaneous tumors in other species. To date, no cases of auricular non-epithelial cutaneous neoplasms erased in a contest of [...] Read more.

The photoinduced etiopathology of actinic keratosis and squamous cell carcinoma in feline species is well known. This etiology has also been reported for non-epithelial cutaneous tumors in other species. To date, no cases of auricular non-epithelial cutaneous neoplasms erased in a contest of actinic keratosis in cats have been reported. The aim of this study was to describe feline auricular non-epithelial cutaneous neoplasms associated with typical UV-induced cutaneous lesions and solar elastosis. The study was conducted on five feline cases diagnosed with auricular non-epithelial cutaneous tumors (two fibrosarcomas, one mixosarcoma, one epithelioid melanoma and one hemangiosarcoma), selected from the Tumor Registry of the Department of Veterinary Sciences of the University of Pisa (1998–2018). Ten and six feline auricular biopsies of normal skin and skin with actinic keratosis, respectively, were used as controls. Orcein stain was used to investigate solar elastosis. Histological changes related to chronic solar irradiation were documented in the skin adjacent to the neoplastic lesions in the five cats. Considering the anatomical localization and the results of histopathology, this study suggests that non-epithelial cutaneous neoplasms may have a UV-induced etiopathogenesis in the feline species. Full article

(This article belongs to the Special Issue Comparative Pathology of Cancers in Animals)

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