An Evaluation of the Flow Cytometric Nuclear DNA Analysis of Intrahepatic Multinodular Hepatocellular Carcinoma for a Diagnosis of Their Multicentricity

This study aims to evaluate the clinical significance of the nuclear DNA index (DI) for identification of multicentrically occurring (MC) hepatocellular carcinoma (HCC). In 14 multinodular HCC patients, the DI of 30 HCC specimens and 14 non-cancerous liver tissues were analyzed by flow cytometry. Histological studies of the 30 HCCs revealed MC in 6 cases and intrahepatic metastasis (IM) in 7 cases except for a histologically undetermined case who was found to be a hepatitis B virus (HBV) carrier, and the MC of this case was determined by a clonal study using the HBV integration pattern. In four of the seven specimens with MC HCC, the DI of all the intrahepatic tumors was 1.0 (diploid pattern), while the remaining three were different. On the other hand, five of the seven IM cases were identical (3 diploid and 2 aneuploid), one similar level (DI = 1.17-1.18) and one different (1.0 and 1.24). Moreover, in one IM case, the possibility of an alteration of the DI during the course of HCC development was investigated. Although the DI of the recurrent main tumor (DI = 1.17) of this case, which was identified as metastasis of the primary tumor by a clonal study, was also similar to that of subsequent metastatic lesions (DI = 1.18), the DI of the primary tumor was 1.0. These results indicate that DI analysis was not enough to make a differential diagnosis of the multicentric occurrence of HCC.