Immunohistochemical Detection of the Placental Form of Glutathione S-Transferase in Dysplastic and Neoplastic Human Uterine Cervix Lesions¹

Expression of the human placental form of glutathione S-transferase (GST-π) in dysplasia (53 cases), carcinoma in situ (10 cases), and invasive carcinoma (46 cases) of human uterine cervix was investigated immunohistochemically with specific anti-GST-π rabbit antibody. While normal squamous epithelium was largely negative, the binding of antibody was appreciable in mild and moderate dysplasias, especially in the cytoplasm of cells demonstrating koilocytotic atypia. In severe dysplasia, the nuclei as well as the cytoplasm were strongly stained in all cell layers except for the superficial layer, and in carcinoma in situ both of them were also strongly stained in all cell layers. In invasive carcinoma, over 90% of cases exhibited strong cytoplasmic staining and in over 70% the nuclei were positive. GST activity towards 1-chloro-2,4-dinitrobenzene and GST-π protein content were significantly increased in all of 4 squamous cell carcinomas examined as compared to values for normal cervical epithelia. Two-dimensional gel electrophoresis followed by immunoblotting using the GST-π antibody demonstrated that, of many cytoplasmic proteins, only the GST-π subunit was specifically bound. These results indicate that GST-π is a potentially useful immunohistochemical marker for (pre)neoplasia of human uterine cervix. In addition, it was demonstrated that the cells in severe dysplasia, carcinoma in situ, and invasive carcinoma expressing GST-π were often characterized by staining with a monoclonal antibody to the v-H-ras gene product.