TGR5 expression in normal kidney and renal neoplasms
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RESEARCH
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TGR5 expression in normal kidney and renal neoplasms Chaohui Lisa Zhao1, Ali Amin1, Yiang Hui1, Dongfang Yang1 and Weibiao Cao1,2*
Abstract Background: The G protein-coupled bile acid receptor (TGR5) is a cell surface receptor which induces the production of intracellular cAMP and promotes epithelial-mesenchymal transition in gastric cancer cell lines. TGR5 is found in a wide variety of tissues including the kidney. However, the patterns of TGR5 expression have not been well characterized in physiologic kidney or renal neoplasms. We explore the expression of TGR5 in benign renal tissue and renal neoplasms and assess its utility as a diagnostic marker. Methods: Sixty-one renal cortical neoplasms from 2000 to 2014 were retrieved. TGR5 protein expression was examined by immunohistochemistry. TGR5 mRNA was also measured by real-time PCR. Results: In normal renal tissue, TGR5 was strongly positive in collecting ducts, distal convoluted tubules and thin loop of Henle. Proximal convoluted tubules showed absent or focal weak staining. In clear cell renal cell carcinomas (RCCs), 25 of 27 cases (92%) were negative for TGR5 (p < 0.001). TGR5 mRNA was also significantly decreased in clear cell RCCs, suggesting that decreased TGR5 protein expression may be attributable to the downregulation of TGR5 mRNA in these tumors. All 11 papillary RCCs expressed TGR5 with 45% (5/11) exhibiting moderate to strong staining. All chromophobe RCCs and oncocytomas were positive for TGR5 with weak to moderate staining. TGR5 mRNA expression in these tumors was similar to normal kidney. All urothelial carcinomas of the renal pelvis strongly expressed TGR5 including a poorly differentiated urothelial carcinoma with sarcomatoid features. Conclusion: TGR5 is strongly expressed in collecting ducts, distal convoluted tubules and thin loop of Henle. TGR5 protein and mRNA expression were notably decreased in clear cell RCCs and may be helpful in differentiating these tumors from other RCCs. Keywords: G protein-coupled bile acid receptor, TGR5, Renal cell carcinoma, Urothelial cell carcinoma, Oncocytoma
Background Renal malignancies are the 7th most common cancer in men in the US with approximately 14,000 attributable deaths annually [1]. Malignant renal cell carcinomas (RCCs) include clear cell RCCs, papillary RCCs (type 1 and type 2), chromophobe RCCs, collecting duct carcinomas, clear cell papillary RCCs, and others [2]. Benign renal epithelial neoplasms include papillary adenomas, oncocytomas and metanephric adenomas [2]. Overall, RCCs constitute 80–85% of primary renal neoplasms. Urothelial cell carcinoma of the renal pelvis is the second most common * Correspondence: [email protected] 1 Department of Pathology, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, 593 Eddy Street, APC 12, Providence, RI 02903, USA 2 Department of Medicine, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, RI 02903, USA
malignant neoplasm in the kidney [1]. Morphologic s
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