Expression of Fas and Fas ligand reflects the biological characteristics but not the status of apoptosis of intrahepatic cholangiocellular carcinoma.

Although intrahepatic cholangiocellular carcinoma (CCC) is the second most common of hepatic malignancies, there have been few studies evaluating its biological characteristics. We therefore decided to investigate the status of apoptosis and of Fas and Fas ligand expression in this carcinoma. We performed immunohistochemistry for Fas and Fas ligand in 40 CCC cases and evaluated the apoptotic index (AI) by counting the number of morphologically apoptotic cells per 1000 cells. AI was higher in cases with poor differentiation, lymph node metastasis and high Ki-67 labeling index (LI). Fas expression in CCC cells decreased in cases with poor differentiation and high Ki-67 LI. Fas ligand expression in the stromal infiltrating mononuclear cells did not correlate with any clinicopathological features of CCC, but was directly related to Fas expression in CCC cells. Fas ligand was also expressed in CCC cells in 27.5% of the cases and more frequently observed in cases with moderate or poor differentiation and high Ki-67 LI. None of these three parameters correlated with AI. These findings indicate that, in CCC, i) cases showing rapid growth characteristics are less likely to die of Fas-mediated apoptosis and more likely to display counterattack to lymphocytes via Fas ligand expressed by carcinoma cells; ii) stromal mononuclear cells express Fas ligand in response to Fas expression in carcinoma cells; iii) Fas and Fas ligand expression are not related to the status of apoptosis.