Environmental risk factors for the development of oral squamous cell carcinoma in cats.

BACKGROUND: Risk factors for oral squamous cell carcinoma (OSCC) in cats are derived from a single study dated almost 20 years ago. The relationship between inflammation of oral tissues and OSCC is still unclear. OBJECTIVES: To investigate previously proposed and novel potential risk factors for OSCC development, including oral inflammatory diseases. ANIMALS: Hundred cats with OSCC, 70 cats with chronic gingivostomatitis (CGS), 63 cats with periodontal disease (PD), and 500 controls. METHODS: Prospective, observational case-control study. Cats with OSCC were compared with an age-matched control sample of client-owned cats and cats with CGS or PD. Owners of cats completed an anonymous questionnaire including demographic, environmental and lifestyle information. RESULTS: On multivariable logistic regression, covariates significantly associated with an increased risk of OSCC were rural environment (OR: 1.77; 95% CI: 1.03-3.04; P = .04), outdoor access (OR: 1.68; 95% CI: 1.07-2.63; P = .02), environmental tobacco smoke (OR: 1.77; 95% CI: 1.05-3; P = .03), and petfood containing chemical additives (OR: 1.98; 95% CI: 1.04-3.76; P = .04). Risk factors shared with CGS and PD were outdoor access and petfood containing chemical additives, respectively. A history of oral inflammation was reported in 35% of cats with OSCC but did not emerge as a risk factor. CONCLUSIONS AND CLINICAL IMPORTANCE: The study proposes novel potential risk factors for OSCC in cats. Although a history of inflammatory oral disease was not significantly more frequent compared with random age-matched controls, OSCC shared several risk factors with CGS and PD.

Validation of oral brushing as a non-invasive technique for the identification of feline oral squamous cell carcinoma by DNA methylation and TP53 mutation analysis.

Feline oral squamous cell carcinoma (FOSCC) is a frequent and progressively invasive tumour. Early lesions are difficult to recognize based on the sole clinical examination and may be misinterpreted as non-neoplastic. Mutations of TP53 and epigenetic alterations of specific genes are present in FOSCC and may be early detected. Aim of this prospective study was to investigate the DNA methylation pattern of a 17-gene panel and TP53 mutational status of FOSCC cytological samples obtained by oral brushing. Results were compared with a control group, in order to validate this non-invasive procedure for the screening of FOSCC. In FOSCC, the same analyses were carried out on the corresponding histological sample, if available. Thirty-five FOSCC and 60 controls were included. Mutations of TP53 were detected in 17 FOSCC brushings (48%) and in none of the controls (P < .001). Six genes (ZAP70, FLI1, MiR124-1, KIF1A, MAGEC2 and MiR363) were differentially methylated in FOSCC and were included in a methylation score. An algorithm based on TP53 mutational status and methylation score allowed to differentiate FOSCC from controls with a 69% sensitivity and a 97% specificity (accuracy, 86%). In 19 FOSCC histological samples, TP53 mutational status was fully concordant with brushings and a positive methylation score was observed in all cases. These results are promising for the identification of FOSCC by oral brushing, although some factors may limit the accuracy of this technique and further studies are required to assess its reproducibility in clinical practice.

Analysis of DNA methylation and TP53 mutational status for differentiating feline oral squamous cell carcinoma from non-neoplastic mucosa: A preliminary study.

Feline oral squamous cell carcinoma (FOSCC) is characterized by high local invasiveness and early bone lysis. The late diagnosis largely limits the efficacy of therapy and increases treatment-related morbidity. The aim of this exploratory study was to assess the methylation pattern of 10 candidate genes and TP53 mutational status in histologic samples of FOSCC. Results were compared with normal oral mucosa and oral inflammatory lesions, in order to establish a gene panel for FOSCC detection. For 10 cats, the above analyses were also performed on oral brushing samples, in order to explore the utility of these methods for screening purposes. Thirty-one FOSCC, 25 chronic inflammatory lesions and 12 controls were included. TP53 mutations were significantly more frequent in the FOSCC (68%) than in the non-neoplastic oral mucosa (3%; P <.001). Based on lasso regression analysis, a step-wise algorithm including TP53, FLI1, MiR124-1, KIF1A and MAGEC2 was proposed. The algorithm allowed to differentiate FOSCC with 94% sensitivity and 100% specificity (accuracy, 97%). When applying the proposed algorithm on 10 brushing samples, accuracy decreased to 80%. These results indicate that the altered DNA methylation of specific genes is present in FOSCC, together with a significant proportion of TP53 mutations. Such alterations are infrequent in normal oral mucosa and chronic stomatitis in cats, suggesting their involvement in feline oral carcinogenesis and their utility as diagnostic biomarkers. Further studies on a high number of brushing samples will be needed to assess the utility of a screening test for the early detection of FOSCC.

A Clinical, Radiographic and Histological Study of Unerupted Teeth in Dogs and Cats: 73 Cases (2001-2018).

Lack of dental eruption may be accompanied by development of dentigerous cysts and has also been rarely associated with neoplasia. However, little information is available on prevalence of unerupted teeth and associated lesions in dogs and cats. The main objective of this study was to describe the epidemiologic data of canine and feline dental patients with unerupted teeth, and assess the prevalence of associated dentigerous cysts and tumors. Secondary aims included the evaluation of possible factors implicated in cystic development, and description of the histological features of dentigerous cysts. Medical and dental records, intraoral photographs, intraoral radiographs of client-owned dogs and cats with clinically missing teeth examined between 2001 and March 2018 were reviewed. Collected data included signalment, reason for presentation, number, type, depth of inclusion and angulation of unerupted teeth, presence of cystic lesions or tumors, abnormalities affecting involved teeth, histopathological findings, performed treatment and outcome. Seventy-three animals (69 dogs and 4 cats) with 113 unerupted teeth were included. The most frequent unerupted tooth in dogs was the first premolar teeth (78%), followed by the canine and third molar teeth. Dentigerous cysts were diagnosed associated with 48 (44.4%) teeth in dogs and one out of five unerupted teeth in cats. The affected teeth in dogs were predominantly in horizontal inclination (40%) and in soft tissue inclusion (77%). Brachycephalic canine breeds were overrepresented. The only unerupted tooth in boxer dogs was the first premolar tooth (32 teeth). Ninety percentage of boxers with unerupted teeth developed associated lesions (25 dentigerous cysts and one tumor). Two ameloblastomas (one in a dog and one in a cat) and one osteosarcoma (in a dog) were diagnosed in association with three unerupted teeth. Histology was essential in diagnosing two odontogenic cysts not evident on radiographs. In all cases that were followed-up, treatment (i.e., extraction, extraction and surgical curettage, or operculectomy) appeared successful. Untreated dentigerous cysts showed progression at re-examination. None of the unerupted teeth without evidence of cyst at the time of diagnosis showed incipient cystic development. None of the evaluated factors were associated with lack of eruption and/or development of associated lesions.

Prevalence of p53 dysregulations in feline oral squamous cell carcinoma and non-neoplastic oral mucosa.

Squamous cell carcinoma is the most common malignant oral tumor in cats. The late presentation is one of the factors contributing to the detrimental prognosis of this disease. The immunohistochemical expression of the p53 tumor suppressor protein has been reported in 24% to 65% of feline oral squamous cell carcinomas, but no study has systematically evaluated in this tumor the presence of p53 encoding gene (TP53) mutations. The aim of this retrospective study was to determine whether p53 immunohistochemistry accurately reflects the mutational status of the TP53 gene in feline oral squamous cell carcinoma. Additionally, the prevalence of p53 dysregulation in feline oral squamous cell carcinoma was compared with that of feline non-neoplastic oral mucosa, in order to investigate the relevance of these dysregulations in cancer development. The association between p53 dysregulations and exposure to environmental tobacco smoke and tumor characteristics was further assessed. Twenty-six incisional biopsies of oral squamous cell carcinomas and 10 cases each of lingual eosinophilic granuloma, chronic gingivostomatitis and normal oral mucosa were included in the study. Eighteen squamous cell carcinomas (69%) expressed p53 and 18 had mutations in exons 5-8 of TP53. The agreement between immunohistochemistry and mutation analysis was 77%. None of non-neoplastic oral mucosa samples had a positive immunohistochemical staining, while one case each of eosinophilic granuloma and chronic gingivostomatitis harbored TP53 mutations. Unlike previously hypothesized, p53 dysregulations were not associated with exposure to environmental tobacco smoke. These results suggest an important role of p53 in feline oral tumorigenesis. Additionally, the immunohistochemical detection of p53 expression appears to reflect the presence of TP53 mutations in the majority of cases. It remains to be determined if the screening for p53 dysregulations, alone or in association with other markers, can eventually contribute to the early detection of this devastating disease.

An Unusual Case of a Nasal Foreign Body in a Cat with Chronic Nasal Discharge.

This report describes a cat infected with the feline infectious virus and a 1 yr history of unilateral mucopurulent nasal discharge. Intraoral radiography and endoscopic examination revealed the presence of a large fragment of tooth root in the right nasal cavity. The cat had previously undergone maxillary canine tooth (104) extraction. The root was successfully removed by an endoscopic-assisted procedure, and follow-up examination 1 yr later documented complete disappearance of the respiratory signs.

Early healing events around titanium implant devices with different surface microtopography: a pilot study in an in vivo rabbit model.

In the present pilot study, the authors morphologically investigated sandblasted, acid-etched surfaces (SLA) at very early experimental times. The tested devices were titanium plate-like implants with flattened wide lateral sides and jagged narrow sides. Because of these implant shape and placement site, the device gained a firm mechanical stability but the largest portion of the implant surface lacked direct contact with host bone and faced a wide peri-implant space rich in marrow tissue, intentionally created in order to study the interfacial interaction between metal surface and biological microenvironment. The insertion of titanium devices into the proximal tibia elicited a sequence of healing events. Newly formed bone proceeded through an early distance osteogenesis, common to both surfaces, and a delayed contact osteogenesis which seemed to follow different patterns at the two surfaces. In fact, SLA devices showed a more osteoconductive behavior retaining a less dense blood clot, which might be earlier and more easily replaced, and leading to a surface-conditioning layer which promotes osteogenic cell differentiation and appositional new bone deposition at the titanium surface. This model system is expected to provide a starting point for further investigations which clarify the early cellular and biomolecular events occurring at the metal surface.