Jagirdar J, Nonomura A, Patil J, Thor A, Paronetto F
Immunopathology Laboratory, Veterans Administration Medical Center, Bronx, NY.
J Exp Pathol. 1989;4(1):37-46.
Aberrant proto-oncogene expression has been implicated in hepatic cell proliferation, transformation and carcinogenesis using a rat model. To investigate the role of ras p21 product expression in human hepatocellular carcinoma (HCC), we have localized ras p21 in formalin fixed, paraffin-embedded normal and abnormal livers utilizing the avidin-biotin peroxidase method and a monoclonal antibody to ras-gene product p21. A semi-quantitative estimate of p21 expression was performed by serial dilutions of primary antibody. While low dilutions of anti-p21 stained normal hepatocytes, higher dilutions failed to react with normal hepatocytes and these dilutions were used for assessment of p21 enhancement. Increased p21 expression of ras oncogene in HCC occurs in fibrolamellar carcinomas and other better differentiated HCC. Tumor dedifferentiation is associated with an attenuation of p21 expression. Liver adjacent to HCC exhibits p21 enhancement, in contrast to liver surrounding metastatic carcinoma, suggesting increased p21 expression in HCC induction.
利用大鼠模型已表明异常原癌基因表达与肝细胞增殖、转化及致癌作用有关。为了研究ras p21产物表达在人类肝细胞癌（HCC）中的作用，我们采用抗生物素蛋白-生物素过氧化物酶法及针对ras基因产物p21的单克隆抗体，对福尔马林固定、石蜡包埋的正常及异常肝脏中的ras p21进行了定位。通过对一抗进行系列稀释对p21表达进行半定量评估。低稀释度的抗p21可对正常肝细胞染色，而高稀释度则不能与正常肝细胞反应，这些高稀释度用于评估p21增强情况。HCC中ras癌基因的p21表达增加见于纤维板层癌及其他分化较好的HCC。肿瘤去分化与p21表达减弱有关。与转移性癌周围的肝脏相反，HCC邻近的肝脏呈现p21增强，提示HCC诱导过程中p21表达增加。
