Nagamine E, Hirayama K, Matsuda K, Okamoto M, Ohmachi T, Uchida K, Kadosawa T, Taniyama H
1 Sanritsu Zelkova Veterinary Laboratory, Takatsu-ku, Kawasaki, Kanagawa, Japan.
2 Department of Veterinary Pathology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
Vet Pathol. 2017 Sep;54(5):783-791. doi: 10.1177/0300985817707005. Epub 2017 May 11.
Oral and cutaneous tissues are the most frequent origin in canine squamous cell carcinoma (SSC). In SCC, changes in adhesion molecule expression and transition from epithelial to mesenchymal phenotype are thought to be important in development of invasive behavior of neoplastic cells at the leading front of the tumor. We therefore investigated histological invasive front grading and epithelial-mesenchymal transition (EMT) in both oral SCCs and cutaneous SCCs. EMT was assessed by evaluating immunohistochemical expression of E-cadherin, β-catenin, desmoglein, vimentin, and N-cadherin. Regardless of the anatomic location, invasive front grading resulted in higher histological grades than grading of the surface. Most oral SCCs were of significantly higher histologic grade than cutaneous SCCs ( P < .01). Expression of E-cadherin, β-catenin, and desmoglein was significantly lower in oral SCC compared with cutaneous SCC ( P < .01). A significant association was found between invasive front grading and loss of E-cadherin, β-catenin, and desmoglein ( P < .01). Also, vimentin-positive neoplastic cells had low immunoreactivity of these adhesion molecules, and a few of these neoplastic cells were positive for N-cadherin. These results suggest not only E-cadherin and β-catenin but also desmoglein as markers for predicting biological behavior of canine SCC. Depending on their primary sites, EMT correlates with biological behavior and therefore histological grade of canine SCC. We suggest that combining invasive front grading with assessment of immunohistochemical expression of E-cadherin, β-catenin, and desmoglein may allow more accurate prediction of biological behavior of canine SCCs.
口腔和皮肤组织是犬鳞状细胞癌（SSC）最常见的起源部位。在鳞状细胞癌中，黏附分子表达的变化以及从上皮表型向间充质表型的转变被认为在肿瘤前沿肿瘤细胞侵袭行为的发展中起重要作用。因此，我们研究了口腔鳞状细胞癌和皮肤鳞状细胞癌的组织学侵袭前沿分级和上皮-间充质转化（EMT）。通过评估E-钙黏蛋白、β-连环蛋白、桥粒芯糖蛋白、波形蛋白和N-钙黏蛋白的免疫组化表达来评估EMT。无论解剖位置如何，侵袭前沿分级的组织学分级均高于表面分级。大多数口腔鳞状细胞癌的组织学分级显著高于皮肤鳞状细胞癌（P <.01）。与皮肤鳞状细胞癌相比，口腔鳞状细胞癌中E-钙黏蛋白、β-连环蛋白和桥粒芯糖蛋白的表达显著降低（P <.01）。在侵袭前沿分级与E-钙黏蛋白、β-连环蛋白和桥粒芯糖蛋白的缺失之间发现了显著关联（P <.01）。此外，波形蛋白阳性的肿瘤细胞对这些黏附分子的免疫反应性较低，其中一些肿瘤细胞N-钙黏蛋白呈阳性。这些结果表明，E-钙黏蛋白、β-连环蛋白以及桥粒芯糖蛋白不仅可作为预测犬鳞状细胞癌生物学行为的标志物。根据其原发部位，EMT与犬鳞状细胞癌的生物学行为相关，因此也与组织学分级相关。我们建议，将侵袭前沿分级与E-钙黏蛋白、β-连环蛋白和桥粒芯糖蛋白免疫组化表达的评估相结合，可能会更准确地预测犬鳞状细胞癌的生物学行为。
