Canine circumanal gland tumors and epithelial – mesenchymal transition: an immunohistochemical study

Abstract

Circumanal gland (CG) tumors are common neoplasms of older dogs. Of these, only circumanal gland carcinomas show clear metastatic potential, and even so metastases seem to be uncommon. Epithelial-mesenchymal transition (EMT) is a process that facilitates the initial steps of metastasis, and to date it has not been systematically investigated in CG tumors. Insight into the occurrence of this process would be a valuable asset in understanding the biology of these tumors. To test the occurrence of EMT we used three immunohistochemical markers that alter their expression in this process, namely – E-cadherin, N-cadherin, and matrix metalloproteinase-9 (MMP-9). Additionally, we used the Ki-67 marker of proliferation. The samples used consisted of 15 adenomas, 11 epitheliomas, 21 well-differentiated carcinomas, seven poorly differentiated carcinomas, and ten samples of normal CG. The results of N-cadherin were negative for all samples. E-cadherin was highly expressed in all groups, but was slightly lower in semi-malignant and malignant tumors; MMP-9 marking was generally very low, but significantly higher in semi-malignant or malignant tumors when compared to benign or non-neoplastic CG. The index of proliferation (Ki-67) was significantly higher for semi-malignant or malignant CG tumors when compared to benign CG tumors or normal CG. These results show that with an increase in the histologic malignancy of these tumors there is a slight drop in E-cadherin, a slight rise in MMP-9, and a significant increase in Ki-67. Therefore, these results suggest the possibility that EMT occurs within the malignant or even semi-malignant forms of CG tumors, but probably as a rare and late event. Further studies are needed to prove or disprove these statements.