Comparative Oncology and Veterinary Cancer Surveillance

Pets have a crucial role in cancer research. Specifically, dogs and cats share the same environment as their owners and thus may serve as sentinels of naturally occurring tumors that are linked to the exposure to environmental hazards. Quantitative comparison of tumor types may reveal unusual cancer frequencies, providing directions for research and generation of hypotheses of cancer causation in a specific area and identification of risk factors. The aim of this study was to describe the data collected by the pathology-based animal cancer registry, managed by Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise (IZSAM), during 10 years of activity (2014–2023) and to assess its potential epidemiological relevance. Frequencies of tumor topography and morphology in dogs and cats were described, analyzed and compared. Proportional morbidity ratios (PMRs) were calculated, taking into consideration some potential risk factors such as species, breed, sex, diet and living environment. The database comprises 5311 tumors (n = 4719 in dogs and n = 592 in cats), with a higher prevalence in females (67.3% in dogs and 61.2% in cats). The mean age at the first diagnosis of tumors was similar between sexes and slightly lower in dogs compared to cats. PMRs highlighted certain risk and “protective” factors for the development of tumors in specific topography. The risk of developing tumors of the blood and hematopoietic system (PMR = 0.44; 95% CI: 0.21–0.94), skin and subcutaneous tissues (PMR = 0.70; 95% CI: 0.61–0.80), oral cavity and pharynx (PMR = 0.60; 95% CI: 0.24–0.89), urinary organs (PMR = 0.33; 95% CI: 0.11–0.99) and bones, joints and cartilage (PMR = 0.72; 95% CI: 0.22–0.98) was lower in non-neutered male dogs than in neutered male dogs. Non-spayed female dogs had a greater risk of developing tumors of the mammary gland (PMR = 1.75; 95% CI: 1.57–1.96), female sexual organs (PMR = 2.12; 95% CI: 1.01–4.36) and respiratory system (PMR = 2.25; 95% CI: 1.55–6.74) but less risk for cutaneous and subcutaneous tissue tumors (PMR = 0.44; 95% CI: 0.38–0.51) and blood/hematopoietic system tumors (PMR = 0.47; 95% CI: 0.26–0.85) compared to spayed female dogs. Compared with mixed breed, purebred dogs had a significantly greater risk of developing mammary gland tumors (PMR = 1.36; 95% CI: 1.20–1.54) and lower risk for respiratory (PMR = 0.15; 95% CI: 0.07–0.32), gastrointestinal (PMR = 0.63; 95% CI: 0.34–0.94) and oral (PMR = 0.59; 95% CI: 0.36–0.96) neoplasia. Non-neutered male cats had a lower risk of developing skin and subcutaneous tumors (PMR = 0.68; 95% CI: 0.50–0.92) compared with neutered cats. The risk of developing skin and subcutaneous tissues tumors was higher for dogs and cats that lived mostly outdoor (PMR dogs = 1.21; 95% CI: 1.10–1.33; PMR cats = 1.18; 95% CI: 1.08–1.47), while dogs that live mainly indoor had a greater risk to develop mammary gland tumors (PMR = 0.78; 95% CI: 0.68–0.89). Results described herein highlight the fundamental role of animal cancer registration initiatives. These efforts would contribute to the possibility of conducting multicentric collaborative studies to deepen the knowledge of the epidemiology of tumors in dogs and cats from a comparative perspective, thus fulfilling the One Health approach. Full article

Enzootic nasal adenocarcinoma (ENA) is a contagious tumor disease of goats and sheep, which is caused by enzootic nasal tumor virus (ENTV). To better understand the pathogenesis of ENA, this study aimed to establish a goat ENA cell line (ENA-1). The cells have been characterized with regard to morphology, growth rate, ultrastructural features, chromosome number, expression of CK7 and CK18, tumorigenicity, species, and mycoplasma contamination. ENA-1 had an epithelioid cell morphology with an unstable chromosome number under a light microscope. Under an electron microscope, the cell nuclear heterogeneity was not obvious, and there were more intermediate filaments and a small number of immature retrovirus-like particles in the cytoplasm. ENA-1 had strong proliferative potential, and the cell multiplication time was about 36 h, which could make BALB/c nude mice develop tumors. CK7 and CK18 were expressed in the cytoplasm of primary goat tumors, in transplanted tumors from nude mice, and un ENA-1 cells with the same intensity. PCR revealed that ENA-1 continuously carried ENTV-2 up to the 17th generation with no germline contamination or mycoplasma contamination. In conclusion, using a serum-containing culture system, ENA-1 cells were successfully isolated, cultured, and purified from goat tumor tissues. The isolated ENA-1 cells retained robust proliferation potential and maintained their phenotype, indicating the potential application of the ENA-1 cell line as an in vitro model of ENA. Full article

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198–569) and 628 days (95% CI 579–676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282–391 days), and 402 days (95% CI 286–517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs. Full article

Canine mammary tumors represent one of the leading malignant pathologies in female dogs, displaying the importance of efficient therapeutic findings, besides the golden-standard surgery, able to limit the development of the disease. Studies in human cancers demonstrated that Doxorubicin presents a good effect in different biological processes like apoptosis, autophagy, the cell cycle, cell invasion, and the epithelial-to-mesenchymal transition. This study followed the effects of Doxorubicin on two canine mammary cancer cell lines P114 and CMT-U27. Doxorubicin treatment in both cell lines shows an inhibitory effect in cell proliferation and an alteration in expression of the EMT-related genes. The obtained results provide valuable information for revealing the link between Doxorubicin, phenotypic changes, and proliferation dynamics in canine mammary tumor models. Full article

Age-related somatic genomic alterations in hematopoietic cell lines have been well characterized in humans; however, this phenomenon has not been well studied in other species. Next-generation sequencing-based liquid biopsy testing for cancer detection was recently developed for dogs and has been used to study the genomic profiles of blood samples from thousands of canine patients since 2021. In this study, 4870 client-owned dogs with and without a diagnosis or suspicion of cancer underwent liquid biopsy testing by this method. Copy number variants detected exclusively in genomic DNA derived from white blood cells (WBC gDNA-specific CNVs) were observed in 126 dogs (2.6%; 95% CI: 2.2–3.1); these copy number variants were absent from matched plasma cell-free DNA, and from tumor tissue in dogs with concurrent cancer. These findings were more common in older dogs and were persistent in WBC gDNA in over 70% of patients, with little to no change in the amplitude of the signal across longitudinal samples. Many of these alterations were observed at recurrent locations in the genome across subjects; the most common finding was a partial loss on CFA25, typically accompanied by a partial gain on the same chromosome. These early findings suggest that age-related somatic alterations may be present at an appreciable frequency in the general canine population. Further research is needed to determine the clinical significance of these findings. Full article

The avian chorioallantoic membrane (CAM) assay has attracted scientific attention in cancer research as an alternative or complementary method for in vivo animal models. Here, we present a xenograft model based on the ostrich (struthio camelus) CAM assay for the first time. The engraftment of 2 × 10⁶ breast cancer carcinoma MDA-MB-231 cells successfully lead to tumor formation. Tumor growth monitoring was evaluated in eight fertilized eggs after xenotransplantation. Cancer cells were injected directly onto the CAM surface, close to a well-vascularized area. Histological analysis confirmed the epithelial origin of tumors. The CAM of ostrich embryos provides a large experimental surface for the xenograft, while the comparably long developmental period allows for a long experimental window for tumor growth and treatment. These advantages could make the ostrich CAM assay an attractive alternative to the well-established chick embryo model. Additionally, the large size of ostrich embryos compared to mice and rats could help overcome the limitations of small animal models. The suggested ostrich model is promising for future applications, for example, in radiopharmaceutical research, the size of the embryonal organs may compensate for the loss in image resolution caused by physical limitations in small animal positron emission tomography (PET) imaging. Full article

The emergence of immunotherapy for the treatment of human cancers has heralded a new era in oncology, one that is making its way into the veterinary clinic. As the immune system of many animal species commonly seen by veterinarians is similar to humans, there is great hope for the translation of human therapies into veterinary oncology. The simplest approach for veterinarians would be to adopt existing reagents that have been developed for human medicine, due to the potential of reduced cost and the time it takes to develop a new drug. However, this strategy may not always prove to be effective and safe with regard to certain drug platforms. Here, we review current therapeutic strategies that could exploit human reagents in veterinary medicine and also those therapies which may prove detrimental when human-specific biological molecules are used in veterinary oncology. In keeping with a One Health framework, we also discuss the potential use of single-domain antibodies (sdAbs) derived from camelid species (also known as Nanobodies™) for therapies targeting multiple veterinary animal patients without the need for species-specific reformulation. Such reagents would not only benefit the health of our veterinary species but could also guide human medicine by studying the effects of outbred animals that develop spontaneous tumors, a more relevant model of human diseases compared to traditional laboratory rodent models. Full article

The study of the structure and function of the animals’ mammary glands is of key importance, as it reveals pathological processes at their onset, thus contributing to their immediate treatment. The most frequently studied mammary diseases are mastitis in cows and ewes and mammary tumours in dogs and cats. Various imaging techniques such as computed tomography, positron emission tomography, magnetic resonance imaging, and ultrasonographic techniques (Doppler, contrast-enchanced, three-dimensional and elastography) are available and can be applied in research or clinical practice in order to evaluate possible abnormalities in mammary glands, as well as to assist in the differential diagnosis. In this review, the above imaging technologies are described, and the perspectives of each method are highlighted. It is inferred that ultrasonographic modalities are the most frequently used imaging techniques for the diagnosis of clinical or subclinical mastitis and treatment guidance on a farm. In companion animals, a combination of imaging techniques should be applied for a more accurate diagnosis of mammary tumours. In any case, the confirmation of the diagnosis is provided by laboratory techniques. Full article

Melanocytic tumour anatomic location is considered an important prognostic indicator. The cutaneous forms are generally considered benign and may show various biological behaviours. This work reports a rare case of canine cutaneous melanoma showing parietal bone metastasis. Bone invasion in melanocytic tumours is often described in oral or visceral melanomas, but not in cutaneous forms. The patient (dog, male, mixed breed, 12 years) was initially presented for the surgical removal of a cutaneous tumour located on the skin of the carpal region of the right forelimb. Four months after, the patient returned with enlarged lymph nodes and acute respiratory failure. The patient was euthanized due to a decline in physical condition. The necropsy showed metastases in the affected forelimb, regional lymph node, splanchnic organs, parietal bone and meninges. Histopathological examination of tumour tissue samples revealed a mixture of pigmented and non-pigmented spindle and epithelioid melanocytes, while according to immunohistochemistry, the tumours showed a strong immunopositivity for VEGF and MMP-10, and a moderate positivity for MMP-2 expression. This case shows that cutaneous melanocytic tumours may show an aggressive malignant form with positive immunohistochemical reactions for multiple invasiveness factors. Full article

Collision tumors (CT) consist of two independent neoplasms with distinct neoplastic populations. Disorders of sexual development (DSDs) are characterized by atypical sexual development leading to various abnormalities of the genital tract. Sex reversal (SR) syndromes are a type of DSD characterized by a discrepancy between chromosomal sex and gonadal development (testes/ovaries) and the presence or the absence of the SRY gene. A phenotypically female 8-year-old Jack Russell terrier dog was referred due to anomalous vaginal discharge and non-pruritic cutaneous bilateral symmetrical alopecia on the flanks. During abdominal palpation, a voluminous mass was detected in the left quadrant area, later confirmed by ultrasound. The owner decided to proceed with euthanasia and necropsy. In the abdominal cavity, the left gonad was increased in size, the right one and the uterus were decreased, and the vagina and vulva appeared to be thickened. Histologically, both gonads were revealed to be testes: the left one was affected by a double neoplastic component (sustentacular tumor and interstitial cell tumor), whereas the right gonad showed coarctated seminiferous tubules. PCR amplification of the genes SRY and AMELX revealed the absence of the MSY region of the Y chromosome. To the authors’ knowledge, this is the first report describing a case of a testicular collision tumor in a DSD SRY-negative dog. Full article