A Streptozotocin-Induced Mouse Model of Renal Tumors: Histopathological and Immunohistochemical Comparisons With Human Chromophobe Renal Cell Carcinoma.

Abstract

Streptozotocin (STZ) is known to induce renal tumors in rodents, but their similarity to human tumors remains poorly defined. We characterized and comparatively validated a mouse model of STZ-induced renal tumorigenesis by administering a single intraperitoneal dose of STZ (250 mg/kg) to female CBA/NSlc mice and maintaining them for 182 days. Renal tumors developed in 25 of 28 surviving mice (89%), with mean and median numbers of 3.4 and 2.5 tumors per animal, respectively. Histopathologically, the tumors were diagnosed as adenomas or adenocarcinomas and exhibited clear, eosinophilic, or mixed cytoplasm. Immunohistochemical analysis of four representative adenocarcinomas revealed positivity for CK AE1/AE3, CK7, PAX8, CD10, CD82, E-cadherin, CD117, and S100A1, and negativity for CK20 and vimentin. These morphological and immunohistochemical features resembled those of human chromophobe renal cell carcinoma (chRCC). Furthermore, the tumors expressed collecting duct markers (uromodulin, CD15, MUC1, and GLUT-1) but lacked proximal convoluted tubule markers (AQP1 and megalin), suggesting a collecting duct origin. Taken together, STZ-induced mouse renal tumors closely resemble human chRCC, providing a reproducible model for investigating the biology and potential therapeutic approaches for this tumor type.