Immunohistochemical Expression Profiles of Cell Adhesion Molecules, Matrix Metalloproteinases and their Tissue Inhibitors in Central and Peripheral Neoplastic Foci of Feline Mammary Carcinoma

Abstract

Feline mammary carcinoma (FMC) is a common cancer with high metastatic potential and high mortality rate. Loss of cell-cell interactions and degradation of the extracellular matrix by proteinases enhances tumour invasion and metastasis. Peripheral neoplastic foci (PNF) are defined as the presence of discrete tumour cell clusters, splitting off from central neoplastic foci (CNF) and lodging around these CNF. PNF therefore locate at the tumour-host interface at the site of invasion. The aim of this study was to evaluate immunohistochemically the expression of cell adhesion molecules (e-cadherin [CDH-1], syndecan 1 [SDC-1] and nectin-2), matrix metalloproteinases (matrix metalloproteinase [MMP]-2, MMP-7 and MMP-9) and their tissue inhibitors (tissue inhibitor of matrix metalloproteinase [TIMP]-1 and TIMP-2) together with the cellular proliferation marker, Ki67, in CNF and PNF of FMCs of different clinical stages and histological grades. Compared with control sections from areas of mammary gland hyperplasia, lower expression of MMP-7 and TIMP-2 was observed in all stages. Increased expression of TIMP-1 was observed in PNF in early-stage disease with no metastasis, while marked expression of CDH-1 and Ki67 occurred in late-stage FMC. In addition, the expression of MMP-2, MMP-9 and TIMP-1 in PNF of tumours with high histological grade (grade III) was higher than in low-grade tumours. The observed divergent protein expression in PNF could potentially form the basis of acting as novel markers in FMC. Potential markers may include the expression of TIMP-1 in PNF in early stage lesions, the expression of CDH-1 and Ki67 in late stages and the expression of MMP-2, MMP-9 and TIMP-1 in high-grade tumours.