Cell kinetic and morphological studies of human cholangiocellular carcinoma

We investigated the cell kinetics and morphologies of cholangiocellular carcinoma (CCC) using 48 autopsied or surgically resected cases (47 were adenocarcinoma and the remaining adenosquamous cell carcinoma), all of which were formalin-fixed and paraffin-embedded. Cell kinetics were analyzed by counting the number of argyrophilic nucleolar organizer regions (AgNOR) using immunostaining of proliferating cell nuclear antigens (PCNA) and flow cytometric DNA analysis. Dedifferentiation of CCC was positively correlated with AgNOR number (2.22 +/- 0.21 in well differentiated, 3.66 +/- 0.85 in moderately differentiated and 4.17 +/- 0.49 in poorly differentiated adenocarcinomas, respectively). In 22 cases, the labeling index (LI) of PCNA was higher in moderately and poorly differentiated adenocarcinomas (24.0 +/- 2.35 and 26.0 +/- 4.89, respectively) than in well differentiated ones (10.8 +/- 2.14). A majority of well differentiated ones were diploid, while aneuploidy prevailed in moderately to poorly differentiated ones. These data suggest that cell proliferative indices and nuclear DNA analysis of CCC accurately reflect their histological grading. The anatomical location of CCC along the biliary tree had no relation to either of the cell kinetic data. In autopsy cases, the patients with organ and lymph node metastases tended to show a higher DNA index and aneuploidy. This study implies that a combination of several cell kinetic data is valuable for the evaluation of the biological behaviors of CCC, and also supports further studies of cell kinetics of CCC using small-sized biopsy specimens, as a prognostic indicator.