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J Korean Soc Transplant. 2013 Sep;27(3):114-120. Korean. Original Article.
Lim BJ , Kim JH , Jeong HJ .
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.

BACKGROUND: Tissue microarray analysis (TMA) is a high-throughput method for histologic evaluation, immunohistochemistry, and in situ hybridization using paraffin embedded tissue. Despite its high efficiency as an experimental tool, TMA is limited because it only contains a very small tissue fragment from each case. Therefore, the purpose of this study was to evaluate the validity of TMA in a study of nephrotoxicity caused by immunosuppressants. METHODS: Male Sprague-Dawley rats were treated with vehicle (n=16), cyclosporine (n=23), and cyclosporine plus losartan (n=13) for a maximum of 7 weeks. After animal sacrifice, renal tissues were embedded in paraffin and processed into slides for microscopic examination using conventional methods and the TMA technique. Acute tubular injury, vascular hyaline change, and interstitial fibrosis were scored in both conventional and TMA slides. The number of interstitial macrophages was counted after ED-1 immunohistochemistry and the results also compared between conventional and TMA slides. RESULTS: The degree of acute tubular injury and interstitial fibrosis showed a significant agreement between conventional and TMA methods (kappa value, 0.79 and 1.00, respectively). The number of interstitial macrophages counted in conventional and TMA slides showed a significant correlation as well (r=0.934, P<0.001). However, the degree of vascular hyaline changes showed less agreement between conventional and TMA methods (kappa value, 0.40). CONCLUSIONS: TMA is a useful and reliable method for the study of nephrotoxicity induced by immunosuppressive agents. TMA also reflects the findings of conventional methods, especially for acute and chronic tubular and interstitial changes.

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