Immunohistochemical Study of the Expression of p53, Pan-ras, c-erbB-2 and PCNA in N-Nitrosomorpholine(NNM)-Induced Hepatocellular Carcinoma of Rats

Kim, Ok Kyung; Shin, Ryun Jo

Abstract

The focus of this study was o aialyze the morphologic expression of p53, Pan-ras, c-erbB-2, and PCNA in preneoplastic and neoplastic liver lesions induced with NNM of rats. The development of hepatocellular tumors was investigated by histology and electron microscope in 65 Splague-Dawley rats administered with NNM in drinking water at low dose(5 mg/100 ml) and high dose(20 mg/100 ml). Three types of hepatocytic degeneration glycogenotic, eosinophilic and basophilic changes were followed by the appearance of hepatocellullar carcinoma. Hepatocellular carcinoma was increased in number and size according to NNM dosage and to duration of exposure. The histological classifications of hepatocelular carcinoma wer trabecular type, which was which was the most common, large eosinophilic, small cell, adenocarcinomatous and clear cell type. The expression of p53, Pan-ras, c-erbB-2 PCNA was examined by immunohistochemical stains. Eosinophilic degeneration revealed mild positivity at 18-26 weeks for expression of all oncogenic proteins studied and PCNA, whereas precancerous lesions showed variable expression from negative to moderate positivity on PCNA. Hepatocellular carcinoma lesions showed strong positivity for all stains and increased intensity during experimental period. These may indicate that chemical carcinogen produce hepatic eosinophilic degeneration and preCancerOus lesions by genetic mutation, resulting in hepatocellular carcinoma.