Proliferating cell nuclear antigen expression in peribiliary glands of stone-containing intrahepatic bile ducts

All cases of hepatolithiasis showed features of chronic proliferative chola ngitis, and it has been speculated that the atypical glandular proliferatio n might be a precursor to overt cholangiocarcinoma. Proliferative cell nucl ear antigen (PCNA) is a nuclear protein synthesized in the G(1)/S phase of the cell cycle and therefore is related to cell proliferative activity. In an attempt to assess the activity of cell proliferation of stone-containing intrahepatic bile ducts, we conducted a study using immunohistochemical st aining with monoclonal antibody to score PCNA in intrahepatic bile ducts. T hirty patients (10 men, 20 women; mean age 52.4 years) having hepatolithias is surgically resected were studied. Ten stone-free patients served as cont rols. All 40 specimens were immunostained for PCNA using PC 10 monoclonal a ntibody. PCNA of both stone-containing and stone-free intrahepatic bile duc ts were assessed by counting positive staining nuclei per 500 cells and exp ressed as labeling index (LI), ie, percentage of positive nuclei to the tot al number of nuclei. The PCNA LI in stone-free intrahepatic bile ducts was generally low: 10.0 +/- 13.2%, 10.4 +/- 10.7% and 7.9 +/- 9.6% for extramur al glands, intramural glands, and epithelial lining, respectively. In contr ast, the PCNA LI for stone-containing intrahepatic bile ducts were signific antly higher than those of controls (P < 0.001): 49.4 +/- 8.3%, 40.6 +/- 7. 0% and 34.1 +/- 6.8% for extramural glands, intramural glands, and epitheli al lining, respectively. The extramural glands had a significantly higher P CNA LI (P < 0.001) than the intramural glands and controls. Hyperplasia was found in all specimens, while dysplasia was found in six of 30 cases with hepatolithiasis. The dysplastic cells also had a higher PCNA LI (P < 0.001) than the hyperplastic cells and normal epithelium. Our findings showed tha t there is marked increase of activity of cell proliferation in stone-conta ining intrahepatic bile ducts. It is well known that genetic mutations are facilitated in proliferating cells. Therefore, our results suggest that the high epithelial turnover in dysplastic cells and extramural glands had hig her potential for proliferation and neoplastic transformation in long-stand ing untreated hepatolithiasis.