Premalignant Changes Identified by Enzyme-Histochemistry with Methacrylate Sections

The development of cancer is characterized by a long latency between the initial exposure to a carcinogenic substance and the final appearance of a macroscopic tumor. Histochemistry has provided the means to identify specific cells involved in this process and many of the changes that take place during the transformation of normal cells to malignant ones. Putative premalignant lesions have been studied extensively in liver carcinogenesis. Histological sections of grossly normal appearing liver a few weeks after treating animals with carcinogen contain discrete areas or “islands” of aberrant enzyme activity that can be detected with enzyme histochemistry and are commonly called “enzyme-altered foci.” These foci display altered activity of one or more enzymes; one of the most common is increased γ-glutamyl transpeptidase (GGT) activity. Since the activities of most enzymes are destroyed by the heat and solvents used for paraffin-embedding, most of this work was done with frozen sections that are often 10 μm in thickness