Increased ubiquitin immunoreactivity in hepatocellular carcinomas and precancerous lesions of the liver

Takuya Osada, Michiie Sakamoto, Hideki Nishibori, Keiichi Iwaya, Yoshihiro Matsuno, Tetsuichiro Muto, Setsuo Hirohashi

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Background/Aims: Ubiquitin covalently attaches to abnormal and short- lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Increased ubiquitin immunoreactivity was recently observed immunohistochemically in human malignant tumors. To clarify the change in protein metabolism during hepatocarcinogenesis, we studied ubiquitin immunoreactivity in hepatocellular carcinomas (HCCs) and precancerous lesions using immunohistochemistry and immunoblot analysis. Methods: A total of 72 HCCs (37 advanced, 19 early, 16 early-advanced (advanced HCC component in early HCC nodule) type HCCs) and 18 precancerous lesions (8 atypical adenomatous hyperplasias (AAHs), 10 adenomatous hyperplasias (AHs)) were studied immunohistochemically. Immunoblot analysis was also performed in advanced HCC and early HCC cases. Results: Non-tumorous hepatocytes were either immunonegative or weakly stained in their nuclei. Advanced HCCs showed strong immunoreactivity in most cases, while early HCCs showed relatively weaker immunoreactivity. In 14 of 16 early-advanced type tumors, the inner portion of the nodules, which corresponds to advanced HCC, showed stronger immunoreactivity than the outer low-grade portion. In 8 of 8 AAHs and 7 of 10 AHs, positive but weak staining was found. Immunoblot analysis showed an increase in 42 kDa ubiquitinated protein(s) in 8 of 16 advanced HCC cases (50%) and in 1 of 6 early HCC cases (16.7%), as well as an increase in several other bands in tumor tissues. Conclusions: The intensity of ubiquitin staining appeared to increase in a stepwise manner from AH to advanced HCC, and the results suggest a possible correlation between changes in the ubiquitinated proteins and multistep hepatocarcinogenesis.

Original languageEnglish
Pages (from-to)1266-1273
Number of pages8
JournalJournal of Hepatology
Issue number6
Publication statusPublished - 1997 Jul
Externally publishedYes


  • Adenomatous hyperplasia
  • Heat-shock protein 72
  • Hepatocellular carcinoma
  • Immunoblot analysis
  • Immunohistochemistry
  • Ubiquitin

ASJC Scopus subject areas

  • Hepatology


Dive into the research topics of 'Increased ubiquitin immunoreactivity in hepatocellular carcinomas and precancerous lesions of the liver'. Together they form a unique fingerprint.

Cite this