Calprotectin and β-Catenin Expression in Canine Hepatoid Gland Tumors and Correlation with Macrophage Infiltration

Abstract

β-catenin is deregulated in cancer malignancies and drives the epithelial-to-mesenchymal transition (EMT). Calprotectin plays antioxidant activities, modulates inflammation and immune responses, and influences cell migration and invasion. Calprotectin can contribute to the progression of various types of cancer. Macrophages expressing calprotectin (MAC387) have been related to M1 polarization and promote EMT. In this study, β-catenin and calprotectin expression in canine hepatoid gland tumors and its relationship with MAC387-positive macrophages is reported. Β-catenin was membranous and strong in hyperplasia and adenomas, moderate or weak in well-differentiated carcinomas, and absent in less-well-differentiated carcinomas. In cells with squamous differentiation, β-catenin was weak or absent. In benign and malignant lesions, MAC/387 positivity was found in both macrophages and clusters of cells with squamous differentiation arranged in whorls centered on ductal-like spaces. These clusters were more voluminous in carcinomas, sometimes with a center of lamellar keratin (horny pearls) and were surrounded by neoplastic hepatoid cells variably positive to calprotectin. The number of calprotectin-positive macrophages progressively increased in the stroma of carcinomas. These findings suggest that hepatoid glands are a useful model for studying the different roles of β-catenin and calprotectin in the tumor milieu and their involvement in tumor differentiation and EMT.