Department of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia, Bologna, Italy.
"M. Malpighi" Section of Anatomic Pathology, Department of Biomedical and Neuromotor Sciences, Bellaria Hospital, University of Bologna, Bologna, Italy.
PLoS One. 2019 Apr 18;14(4):e0215621. doi: 10.1371/journal.pone.0215621. eCollection 2019.
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.
鳞状细胞癌是猫最常见的恶性口腔肿瘤。晚期表现是导致这种疾病预后不良的因素之一。已经报道了猫口腔鳞状细胞癌中 p53 肿瘤抑制蛋白的免疫组织化学表达在 24%至 65%之间,但尚无研究系统地评估过这种肿瘤中 p53 编码基因(TP53)突变的存在。本回顾性研究的目的是确定 p53 免疫组织化学是否准确反映了猫口腔鳞状细胞癌中 TP53 基因的突变状态。此外,还比较了猫口腔鳞状细胞癌中 p53 失调的流行率与猫非肿瘤性口腔黏膜中的流行率,以研究这些失调在癌症发展中的相关性。还进一步评估了 p53 失调与暴露于环境烟草烟雾和肿瘤特征之间的关联。本研究纳入了 26 例口腔鳞状细胞癌的切取活检样本和 10 例每例的舌嗜酸粒细胞肉芽肿、慢性龈口炎和正常口腔黏膜。18 例(69%)鳞状细胞癌表达 p53,18 例有 TP53 外显子 5-8 的突变。免疫组织化学和突变分析之间的一致性为 77%。非肿瘤性口腔黏膜样本均无阳性免疫组织化学染色,而嗜酸粒细胞肉芽肿和慢性龈口炎各有 1 例存在 TP53 突变。与之前的假设不同,p53 失调与暴露于环境烟草烟雾无关。这些结果表明 p53 在猫口腔肿瘤发生中起重要作用。此外,p53 表达的免疫组织化学检测似乎反映了大多数情况下 TP53 突变的存在。尚待确定是否单独或与其他标志物一起筛查 p53 失调最终能否有助于早期发现这种毁灭性疾病。