Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Calle 60 y 118, La Plata, Buenos Aires, Argentina; Facultad de Ciencias Veterinarias, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de La Plata, Calle 60 y 118, La Plata, Buenos Aires, Argentina.
Laboratorio de Patología Especial Veterinaria Dr. Bernardo Epstein, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Calle 60 y 118, La Plata, Buenos Aires, Argentina.
J Comp Pathol. 2020 Apr;176:1-9. doi: 10.1016/j.jcpa.2020.01.006. Epub 2020 Feb 26.
Clinically relevant epidermal tumours in dogs include cutaneous papillomas (CPs) and cutaneous squamous cell carcinomas (CSCCs). The development of CPs and CSCCs involves dysregulation in expression of E-cadherin/β-catenin; however, knowledge about the contribution of these molecules to epidermal tumourigenesis in dogs is limited. This study examined the immunohistochemical expression pattern of E-cadherin/β-catenin in samples of normal canine epidermis, CPs, preneoplastic epidermis and CSCCs, using tissue microarrays, in order to elucidate whether the dysregulated expression of these molecules may contribute to the pathogenesis of clinically relevant epidermal tumours in dogs. We also investigated the correlation between the immunohistochemical expression pattern of E-cadherin/β-catenin in these tissue microarrays to further evaluate whether the disruption of the adherens junction interactions plays a relevant role in canine epidermal tumourigenesis. In samples of CP and preneoplastic epidermis, the membrane immunoreactivity of E-cadherin/β-catenin was conserved, while in CSCC, the immunoreactivity of these molecules was significantly reduced, independently of the tumour location. There was significant correlation between the membrane expression of E-cadherin/β-catenin in CSCC. β-catenin also showed cytoplasmic and nuclear expression in samples of CP, preneoplastic epidermis and CSCC. These results support the hypothesis that dysregulated expression of E-cadherin/β-catenin may play a critical role in the pathogenesis of relevant canine epidermal tumours, not only due to the disruption of the intercellular adherens junctions, but also due to the dysregulated activity of the signalling pathways in which these molecules are involved.
临床上相关的犬类表皮肿瘤包括皮肤乳头状瘤（CPs）和皮肤鳞状细胞癌（CSCCs）。CPs 和 CSCCs 的发展涉及 E-钙黏蛋白/β-连环蛋白表达的失调；然而，关于这些分子对犬表皮肿瘤发生的贡献的知识是有限的。本研究使用组织微阵列检查了正常犬表皮、CP、癌前表皮和 CSCC 样本中 E-钙黏蛋白/β-连环蛋白的免疫组织化学表达模式，以阐明这些分子的失调表达是否可能有助于犬临床上相关的表皮肿瘤的发病机制。我们还研究了这些组织微阵列中 E-钙黏蛋白/β-连环蛋白免疫组织化学表达模式之间的相关性，以进一步评估黏着连接相互作用的破坏是否在犬表皮肿瘤发生中起相关作用。在 CP 和癌前表皮样本中，E-钙黏蛋白/β-连环蛋白的膜免疫反应性得以保留，而在 CSCC 中，这些分子的免疫反应性显著降低，与肿瘤位置无关。CSCC 中 E-钙黏蛋白/β-连环蛋白的膜表达之间存在显著相关性。β-连环蛋白还在 CP、癌前表皮和 CSCC 样本中显示出细胞质和核表达。这些结果支持这样一种假设，即 E-钙黏蛋白/β-连环蛋白的失调表达可能在相关犬类表皮肿瘤的发病机制中起关键作用，不仅由于细胞间黏着连接的破坏，还由于这些分子参与的信号通路的失调活性。
