Neoplastic Transformation of the Colon Mucosa Correlates with an Altered Expression of RAAS in Dogs

Abstract:

Background: Tissue effects of the renin-angiotensin-aldosterone system (RAAS) include the regulation of cell growth and proliferation, and RAAS imbalances have been linked to cancer development and progression. RAAS components have potential as diagnostic/prognostic markers and therapeutic targets. Colonic adenomatous lesions are precursors of colorectal cancer, providing a model for carcinogenesis research.Animals: Archived colon tissues from 26 dogs.

Methods: For each polyp (based on dysplasia/necrosis assessed as grade I: n=10, grade II: n=9, grade III: n=7) and adjacent untransformed mucosa, inflammation/structural changes, goblet cells (Alcian/Pas+), mitotic index (Ki67+), apoptosis rate (TUNEL assay), and the immunohistochemical expression of the main RAAS receptors (AT1R, AT2R, and MAS1) and mineralocorticoid receptor (MCR) were scored, tested for correlations, and compared among differentiation grades.

Results: Higher-grade polyps had more goblet cells (P=0.004) and more marked inflammation/structural lesions, proliferation, and apoptosis in the adjacent mucosa (all P

Conclusions: Local RAAS dysregulation, with overexpression of traditional RAAS and downregulation of alternative RAAS arms, is a feature of adenomatous colonic lesions and is linked to the degree of dysplasia. Its role in angiogenesis, proliferation, epithelial-to-mesenchymal transition, and metastasis warrants further investigation.