Date Published: April 18, 2019
Publisher: Public Library of Science
Author(s): Andrea Renzi, Paola De Bonis, Luca Morandi, Jacopo Lenzi, Debora Tinto, Antonella Rigillo, Giuliano Bettini, Emma Bellei, Silvia Sabattini, Sakamuri V. Reddy.
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.
Squamous cell carcinoma is the most common malignant tumor of the oral cavity in cats, accounting for 60–70% of all oral malignancies. [1–3] Feline oral squamous cell carcinoma (FOSCC) most frequently involves the lingual region and dentate jaws, and may appear either as a necrotic ulcerative lesion or as a firm nodular swelling, generally associated with high local invasiveness and early bone lysis. [2, 3] Although regional and distant metastases have been reported, death most frequently occurs from complications associated with the primary tumor before metastatic disease has an opportunity to become clinically relevant. [3, 4–6] Due to location and rapid tumor progression, diagnosis is often late, and this largely limits the efficacy of treatments, including surgery, radiation therapy and chemotherapy. Prognosis is poor for the majority of cats, and, even with a multimodal therapeutic approach, the median survival time rarely exceeds 12 months. [2, 7, 8]
The complete demographic, histological and molecular data of the cases in this study are provided in S1 and S2 Tables.
There are many similarities at both clinical and molecular level between HNSCC and FOSCC, which has led to the proposal that FOSCC may serve as a spontaneous model for human disease. [22, 32, 33]
These results suggest an important role of p53 in feline oral tumorigenesis. This is supported by a significantly higher prevalence of p53 dysregulation in FOSCC compared with normal oral mucosa and inflammatory lesions. Additionally, the IHC detection of p53 expression appears to reflect the presence of p53 mutations in the majority of cases. It remains to be determined if the screening for p53 dysregulations, alone or in association with other markers, may contribute to the early detection of this detrimental disease, and eventually help to make it more curable.