Proliferative and apoptotic activity in hepatocellular carcinoma and surrounding non-neoplastic liver tissue

Pflugers Arch. 2001;442(6 Suppl 1):R174-6. doi: 10.1007/s004240100014.

Abstract

The aim of the study was to determine the proliferative and apoptotic activity of neoplastic and non-neoplastic hepatocytes, to ascertain whether there was a correlation between the histopathological characteristics of hepatocellular carcinoma (HCC) and its proliferative or apoptotic activity.

Methods: One tumour sample and one sample of non-neoplastic liver from 16 patients with HCC were analysed. The proliferative activity was established by immunohistochemical staining against PCNA (proliferating cell nuclear antigen) and Ki-67. Apoptotic activity was determined by morphological and TUNEL methods. Bcl-2 immunoreactivity was analysed.

Results: A positive correlation between PCNA and Ki-67 proliferative indexes was found in HCC (p < 0.01). The PCNA index was 0.21% +/- 0.80% (Mean +/- SD) in non-neoplastic liver and 7.41% +/- 8.22% in HCC, while the Ki-67 index was 0.19% +/- 0.26% in non-neoplastic liver and 9.67% +/- 7.70% in HCC. The differences between HCC and non-neoplastic liver were significant (p < 0.05). The PCNA index differed significantly between different HCC grades (p < 0.05). In HCC and non-neoplastic liver samples, apoptotic indexes (AI) assessed morphologically were higher than Al determined by the TUNEL method. Differences in Al (irrespective of the method used) between different HCC grades were not significant. Bcl-2 staining was positive in one non-neoplastic liver sample (6.3%) and in 4 HCC samples (25%).

Conclusions: PCNA and Ki-67 were useful for proliferative activity assessment of hepatocytes. There were no differences in apoptotic activity between HCC and non-neoplastic tissue, so it seems that uncontrolled tumour cell division plays an important role in HCC growth. In the regulation of the apoptotic process in HCC, Bcl-2 could be important.

MeSH terms

  • Apoptosis*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Division
  • Hepatocytes / chemistry
  • Hepatocytes / pathology
  • Humans
  • In Situ Nick-End Labeling
  • Ki-67 Antigen / analysis
  • Liver / pathology*
  • Liver Neoplasms / pathology*
  • Proliferating Cell Nuclear Antigen / analysis

Substances

  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen