IN-SITU NUCLEIC-ACID HYBRIDIZATION OF PYRUVATE-DEHYDROGENASE COMPLEX-E2 IN PRIMARY BILIARY-CIRRHOSIS, PYRUVATE-DEHYDROGENASE COMPLEX-E2 MESSENGER-RNA IS EXPRESSED IN HEPATOCYTES BUT NOT IN BILIARY EPITHELIUM

Pyruvate dehydrogenase-E2, or a cross-reactive molecule, has been show n by a variety of immunohistochemical methods to be present in increas ed amounts in biliary epithelial cells (BEG) in primary biliary cirrho sis (PBC), In this study, to further understand the nature of the immu noreactive molecule in BEG, we examined the expression of pyruvate deh ydrogenase complex-E2 (PDC-E2) messenger RNA (mRNA) and PDC-E2 protein in sections of livers from patients and controls to help identify the molecule found in BEG. We performed in situ hybridization using an an tisense probe against the major epitope of PDC-E2. The data were very striking and suggested that there was no increased production of PDC-E 2 in BEG. For example, in livers from patients with PBC, PDC-E2 mRNA w as found in periportal hepatocytes in 16 of 17 cases (94%), In contras t, interlobular bile ducts and septal bile ducts had detectable levels of PDC-E2 mRNA in only 1 of 17 (6%) and 3 of 8 (38%) cases, respectiv ely, Interestingly, proliferating bile ductules contained detectable l evels of mRNA in 12 of 15 cases (80%), In control liver, periportal he patocytes were positive in 15 of 17 cases (88%), Interlobular bile duc ts, septal bile ducts, and proliferating bile ductules expressed mRNA signals in 4 of 17 (24%), 2 of 10 (20%), and 14 of 16 (88%), respectiv ely, When formalin-fixed, paraffin-embedded sections were examined by immunohistochemical staining with anti-PDC-E2 monoclonal antibody (mAb ) C355.1, the interlobular bile ducts showed typical aberrant apical s taining in all 10 PBC cases, but 0 of 9 liver controls, Periportal hep atocytes, proliferating bile ductules and infiltrating mononuclear cel ls stained with C355.1 but in a characteristic mitochondrial staining pattern, The presence of a PDC-E2-like molecule recognized by C355.1 i s not reflected by the expression levels of PDC-E2 mRNA in the BEC of patients with PBC.