DNA fragmentation and cell proliferation correlated with tumor grade in patients with hepatocellular carcinoma.

Abstract

DNA fragmentation and cell proliferation in patients with hepatocellular carcinoma (HCC) have not been well described on fine-needle aspiration biopsies (FNABs). To investigate the contribution of apoptosis, a major mechanism of cell death, to the growth of HCC, the authors analyzed both apoptosis and cell proliferation in patients with HCC. The authors studied 50 tumors from 50 patients with HCC: Ten tumors were well-differentiated HCC, 24 tumors were moderately differentiated HCC, and 16 tumors were poorly differentiated HCC. The detection of DNA fragments in situ using the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay was applied to investigate active cell death (apoptosis), and the MIB-1 antigen was used to investigate cell proliferation. The TUNEL indices were 0.34 +/- 0.08, 082 +/- 0.30, and 2.0 +/- 0.95 in well-differentiated HCC, moderately differentiated HCC, and poorly differentiated HCC, respectively. The MIB-1 antigen labeling indices were 6.7 +/- 0.10, 13.2 +/- 3.4; and 26.9 +/- 6.5, respectively, in the same order of tumor differentiation. The differences in both TUNEL and MIB-1 labeling indices were significant between well differentiated HCC, moderately differentiated HCC, and poorly differentiated HCC, and a positive correlation was found between the TUNEL indices and the MIB-1 indices. Apoptosis (cell death) and cell proliferation increase as the grade of differentiation decreases in HCC, suggesting a rapid turnover of tumor cells in tumors with lower grades of differentiation, and apoptosis may play an important role in the growth of tumors in patients with HCC.