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15 pages, 5055 KiB

Open AccessArticle

Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas

by Julia M. Grassinger, Sophie Merz, Heike Aupperle-Lellbach, Hanna Erhard and Robert Klopfleisch

Vet. Sci. 2019, 6(1), 31; https://doi.org/10.3390/vetsci6010031 - 19 Mar 2019

Cited by 16 | Viewed by 6412

Abstract

The presence of BRAF variant V595E, as well as an increased cyclooxygenase-2 (COX-2) expression in canine transitional cell carcinoma (TCC) are well-described in the literature. The aim of the present study was to investigate the correlation between breed (terrier versus non-terrier dogs), histological [...] Read more.

The presence of BRAF variant V595E, as well as an increased cyclooxygenase-2 (COX-2) expression in canine transitional cell carcinoma (TCC) are well-described in the literature. The aim of the present study was to investigate the correlation between breed (terrier versus non-terrier dogs), histological grade, COX-2 expression, and BRAF mutation in canine TCC. Therefore, transmural TCC biopsies from 65 dogs (15 terriers, 50 non-terriers) were graded histologically into low- and high-grade. Immunohistochemical evaluation of the intensity of COX-2 expression was performed using an immunoreactive score (IRS). Exon 15 of chromosome 16 was examined for the BRAF variant c.1799T>A by TaqMan^® SNP assay. TCC was low-grade in 20 cases (one terrier, 19 non-terriers) and high-grade in 45 cases (14 terriers, 31 non-terriers). Contrary to humans, histological grade was not significantly correlated to the intensity of COX-2 expression. BRAF mutation was detected in 11/15 (73%) TCC of terriers and in 18/50 (36%) TCC of non-terriers. Histological grade and BRAF mutation were not correlated significantly (p = 0.2912). Terriers had a considerably higher prevalence of high-grade tumors (p < 0.0001), as well as of BRAF mutation (p ≤ 0.05) compared to non-terriers. In non-terriers, neoplasms with BRAF mutation showed a significantly higher intensity of COX-2 expression than those without BRAF mutation (p ≤ 0.05). In conclusion, in contrast to humans, testing for BRAF mutation in canine TCC is a sensitive diagnostic method especially in terriers (73%) and may be recommended as a screening test. However, evidence of BRAF mutation in canine TCC is not a predictor for the histological grade. Moreover, a positive correlation between histological grade and the intensity of COX-2 expression was not found. Further studies are necessary to clarify the clinical and prognostic relevance of the elevated intensity of COX-2 expression of TCC with BRAF mutation detected in non-terriers. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

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11 pages, 1982 KiB

Open AccessArticle

Characterization of Collagen Fibers (I, III, IV) and Elastin of Normal and Neoplastic Canine Prostatic Tissues

by Luis Gabriel Rivera Calderón, Priscila Emiko Kobayashi, Rosemeri Oliveira Vasconcelos, Carlos Eduardo Fonseca-Alves and Renée Laufer-Amorim

Vet. Sci. 2019, 6(1), 22; https://doi.org/10.3390/vetsci6010022 - 02 Mar 2019

Cited by 10 | Viewed by 4513

Abstract

This study aimed to investigate collagen (Coll-I, III, IV) and elastin in canine normal prostate and prostate cancer (PC) using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was [...] Read more.

This study aimed to investigate collagen (Coll-I, III, IV) and elastin in canine normal prostate and prostate cancer (PC) using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was analyzed with ImageJ software. The distribution of Coll-I and Coll-III was approximately 80% around prostatic ducts and acini, 15% among smooth muscle, and 5% surrounding blood vessels, in both normal prostate and PC. There was a higher median area of Coll-III in PC when compared to normal prostatic tissue (p = 0.001 for PSR and p = 0.05 for IHC). Immunostaining for Coll-IV was observed in the basal membrane of prostate acini, smooth muscle, blood vessels, and nerve fibers of normal and PC samples. Although there was no difference in Coll-IV area between normal tissue and PC, tumors with Gleason score 10 showed absence of Coll-IV, when compared to scores 6 and 8 (p = 0.0095). Elastic fibers were found in the septa dividing the lobules and around the prostatic acini of normal samples and were statistically higher in PC compared to normal tissue (p = 0.00229). Investigation of ECM components brings new information and should be correlated with prognosis in future studies. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

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12 pages, 1636 KiB

Open AccessArticle

Tumor–Microenvironment Interaction: Analysis of Mast Cell Populations in Normal Tissue and Proliferative Disorders of the Canine Prostate

by Sabrina Vanessa Patrizia Defourny, Mariarita Romanucci, Valeria Grieco, Gina Rosaria Quaglione, Chiara Santolini and Leonardo Della Salda

Vet. Sci. 2019, 6(1), 16; https://doi.org/10.3390/vetsci6010016 - 13 Feb 2019

Cited by 4 | Viewed by 4000

Abstract

Mast cells (MCs) are involved in angiogenesis, tissue remodeling and immunomodulation in several human and animal tumors, although their exact role is still controversial. Since no information is available in canine prostate carcinoma (PC) and normal prostate tissues, the aims of this study [...] Read more.

Mast cells (MCs) are involved in angiogenesis, tissue remodeling and immunomodulation in several human and animal tumors, although their exact role is still controversial. Since no information is available in canine prostate carcinoma (PC) and normal prostate tissues, the aims of this study were to evaluate the possible correlations between MC distribution, molecular expression and microvessel density (MVD) in normal prostatic tissue and proliferative disorders of the canine prostate. All samples (6 normal, 15 benign prostate hyperplasia-BPH, 8 PC) were stained with Toluidine Blue and immunohistochemically evaluated for tryptase, c-Kit (CD117) and CD31. Mast cell density (MCD) and MVD were quantified by the hot-spot method. MCD was significantly increased in periglandular/peritumoral areas, when compared with intraglandular/intratumoral areas, in all groups (p = 0.03). C-Kit expression was strongly associated with PC (ρ = 0.75 p = 0.03), whereas positive correlation between tryptase and c-Kit expression (ρ = 0.64 p = 0.01) was observed in periglandular areas of BPH. MVD showed a correlation with MCD in BPH (ρ = 0.54 p = 0.04). Our data support the importance of c-Kit in regulating MC proliferation. The predominant location of MCs in peritumoral areas of canine PC was similar to the human counterpart, in which PC cells are supposed to produce substances attracting MCs to the tumor microenvironment. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

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12 pages, 1635 KiB

Open AccessArticle

Deregulation of VEGFR-2 and PDGFR Expression and Microvascular Density in a Triple-Negative Model of Canine Malignant Mammary Tumors with Lymph Node or Lung Metastasis

by Denner Santos Dos Anjos, Aline Fernandes Vital, Patrícia de Faria Lainetti, Antonio Fernando Leis-Filho, Fabiola Dalmolin, Fabiana Elias, Sabryna Gouveia Calazans and Carlos Eduardo Fonseca-Alves

Vet. Sci. 2019, 6(1), 3; https://doi.org/10.3390/vetsci6010003 - 09 Jan 2019

Cited by 15 | Viewed by 4103

Abstract

Canine mammary tumors (CMT) represent the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), Platelet-derived [...] Read more.

Canine mammary tumors (CMT) represent the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), Platelet-derived growth factor receptor (PDGFR), and microvascular density (MVD) in a group of metastatic and nonmetastatic triple-negative CMT and compare the expression based on clinical parameters. Twenty-six female dogs with triple-negative mammary tumors were divided into three groups: nonmetastatic tumors (NMT) (n = 11), tumors with lymph node metastasis (LNM) (n = 10), and tumors with lung metastasis (LM) (n = 5). We observed increased VEGFR-2 expression in LNM compared with NMT and a positive correlation between tumor grade and VEGFR-2 expression. A positive correlation was noted between VEGFR-2 and PDGFR expression. Regarding microvascular density (MVD), we identified a higher number of vessels in primary tumors with lymph node metastasis and lung metastasis compared with tumors with no metastasis. The primary tumors with lung metastasis exhibited an increased MVD compared with carcinoma with lymph node metastasis. Overall, our results suggest a deregulation of VEGFR-2 and PDGFR and high MVD in metastatic tumors, indicating a role for angiogenesis in tumor progression. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

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Review

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19 pages, 1909 KiB

Open AccessReview

Risk Factors for Development of Canine and Human Osteosarcoma: A Comparative Review

by Kelly M. Makielski, Lauren J. Mills, Aaron L. Sarver, Michael S. Henson, Logan G. Spector, Shruthi Naik and Jaime F. Modiano

Vet. Sci. 2019, 6(2), 48; https://doi.org/10.3390/vetsci6020048 - 25 May 2019

Cited by 51 | Viewed by 12250

Abstract

Osteosarcoma is the most common primary tumor of bone. Osteosarcomas are rare in humans, but occur more commonly in dogs. A comparative approach to studying osteosarcoma has highlighted many clinical and biologic aspects of the disease that are similar between dogs and humans; [...] Read more.

Osteosarcoma is the most common primary tumor of bone. Osteosarcomas are rare in humans, but occur more commonly in dogs. A comparative approach to studying osteosarcoma has highlighted many clinical and biologic aspects of the disease that are similar between dogs and humans; however, important species-specific differences are becoming increasingly recognized. In this review, we describe risk factors for the development of osteosarcoma in dogs and humans, including height and body size, genetics, and conditions that increase turnover of bone-forming cells, underscoring the concept that stochastic mutational events associated with cellular replication are likely to be the major molecular drivers of this disease. We also discuss adaptive, cancer-protective traits that have evolved in large, long-lived mammals, and how increasing size and longevity in the absence of natural selection can account for the elevated bone cancer risk in modern domestic dogs. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

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9 pages, 623 KiB

Open AccessReview

Cytokine Expression in Canine Lymphoma, Osteosarcoma, Mammary Gland Tumour and Melanoma: Comparative Aspects

by Sergio Erdal Irac, Annika Oksa, Karen Jackson, Aaron Herndon, Rachel Allavena and Chiara Palmieri

Vet. Sci. 2019, 6(2), 37; https://doi.org/10.3390/vetsci6020037 - 02 Apr 2019

Cited by 9 | Viewed by 6602

Abstract

Cytokines released in the tumour microenvironment play a major role in cancer pathogenesis. In human cancers and corresponding animal models, cytokine expression contributes to tumour growth and progression, as well as regulation of the host anti-tumour response. The elucidation of the function and [...] Read more.

Cytokines released in the tumour microenvironment play a major role in cancer pathogenesis. In human cancers and corresponding animal models, cytokine expression contributes to tumour growth and progression, as well as regulation of the host anti-tumour response. The elucidation of the function and importance of cytokines in canine cancers is still in an early stage, although relevant data have been obtained in classical examples of comparative models of human cancers, such as osteosarcoma, melanoma, mammary tumour and lymphoma. A deeper understanding of the cytokine signature may advance diagnosis, prevention and treatment of canine cancers. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

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12 pages, 225 KiB

Open AccessReview

Use of Minimally Invasive Surgery in the Diagnosis and Treatment of Cancer in Dogs and Cats

by Ingrid M. Balsa and William T. N. Culp

Vet. Sci. 2019, 6(1), 33; https://doi.org/10.3390/vetsci6010033 - 20 Mar 2019

Cited by 13 | Viewed by 5849

Abstract

Surgical management of neoplastic disease is common in veterinary medicine. Minimally invasive surgery (MIS) has gained widespread acceptance by veterinary surgeons and is experiencing rapid growth and frequency of use. Many neoplastic diseases in the abdomen and thorax of dogs and cats can [...] Read more.

Surgical management of neoplastic disease is common in veterinary medicine. Minimally invasive surgery (MIS) has gained widespread acceptance by veterinary surgeons and is experiencing rapid growth and frequency of use. Many neoplastic diseases in the abdomen and thorax of dogs and cats can be treated as effectively with MIS as with traditional open surgery. Additionally, MIS allows for less invasive options for organ biopsy in cancer patients either for initial diagnosis or for staging to inform prognosis and treatment. Despite the recent increase in MIS, additional research is required to further characterize the benefits to oncology patients and to ensure that surgical oncologic principles and patient outcomes are not compromised by the use of MIS. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

12 pages, 640 KiB

Open AccessReview

A Review of Immunotherapeutic Strategies in Canine Malignant Melanoma

by Ramón M. Almela and Agustina Ansón

Vet. Sci. 2019, 6(1), 15; https://doi.org/10.3390/vetsci6010015 - 12 Feb 2019

Cited by 24 | Viewed by 9312

Abstract

In dogs, melanomas are relatively common tumors and the most common form of oral malignancy. Biological behavior is highly variable, usually aggressive, and frequently metastatic, with reported survival times of three months for oral or mucosal melanomas in advanced disease stages. Classical clinical [...] Read more.

In dogs, melanomas are relatively common tumors and the most common form of oral malignancy. Biological behavior is highly variable, usually aggressive, and frequently metastatic, with reported survival times of three months for oral or mucosal melanomas in advanced disease stages. Classical clinical management remains challenging; thus, novel and more efficacious treatment strategies are needed. Evidence-based medicine supports the role of the immune system to treat neoplastic diseases. Besides, immunotherapy offers the possibility of a precise medicinal approach to treat cancer. In recent years, multiple immunotherapeutic strategies have been developed, and are now recognized as a pillar of treatment. In addition, dogs represent a good model for translational medicine purposes. This review will cover the most relevant immunotherapeutic strategies for the treatment of canine malignant melanoma, divided among five different categories, namely, monoclonal antibodies, nonspecific immunotherapy activated by bacteria, vaccines, gene therapy, and lymphokine-activated killer cell therapy. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

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17 pages, 354 KiB

Open AccessReview

Lower Urinary Tract Neoplasia

by Maureen A. Griffin, William T. N. Culp and Robert B. Rebhun

Vet. Sci. 2018, 5(4), 96; https://doi.org/10.3390/vetsci5040096 - 27 Nov 2018

Cited by 25 | Viewed by 8209

Abstract

Lower urinary tract neoplasia in companion animals is a debilitating and often life-threatening disease. Tumors of the bladder, urethra, and prostate often occur independently, although extension of these tumors into adjacent regions of the lower urinary tract is documented frequently. The most common [...] Read more.

Lower urinary tract neoplasia in companion animals is a debilitating and often life-threatening disease. Tumors of the bladder, urethra, and prostate often occur independently, although extension of these tumors into adjacent regions of the lower urinary tract is documented frequently. The most common lower urinary tract tumor in dogs and cats is transitional cell carcinoma (TCC). In both dogs and cats, TCC affecting the urinary bladder is generally considered to be highly aggressive with both local and metastatic disease potential, and this disease poses unique treatment challenges. Whereas much literature exists regarding the TCC disease process, treatment options, and prognosis in dogs, relatively few studies on feline TCC have been published due to the lower incidence of TCC in this species. Prostate tumors, most commonly adenocarcinomas, occur less commonly in dogs and cats but serve an important role as a comparative model for prostate neoplasia in humans. This article serves as a review of the current information regarding canine and feline lower urinary tract neoplasia as well as the relevance of these diseases with respect to their human counterparts. Full article

(This article belongs to the Special Issue Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy)

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