Cell proliferation and cell loss in nodule-in-nodule hepatocellular carcinoma.
OBJECTIVE
In order to clarify the significance of the balance between cell proliferation and cell loss during the progression of hepatocellular carcinoma, 16 operative specimens of nodule-in-nodule hepatocellular carcinoma were investigated.


METHODS
In 16 specimens, cell proliferation was evaluated by the expression of Ki-67 nuclear antigen, and cell loss was also examined by the method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The expressions of p53 protein, bcl-2 protein and Fas antigen were also investigated to clarify the relationship between their expression and cell kinetics.


RESULTS
The Ki-67 labeling index of the inner nodules was higher than that for the outer nodules (18.9% vs. 7.2%; p < 0.05) and the TUNEL labeling index of the inner nodules was also higher than that for the outer nodules (12.8% vs. 6.6%; p < 0.05). The increasing rate of the Ki-67 labeling index from Edmondson's grade I to II was 3.9 +/- 3.0, that from grade II to III was 3.9 +/- 2.4, while the increasing rate of the TUNEL labeling index from grade I to II was 2.7 +/- 0.3 and that from grade II to III was 1.7 +/- 0.2 (p < 0.05). p53 Protein was observed in 5 cases, while bcl-2 protein was found in 4 cases in the border area of the inner nodule. However, Fas antigen was found in none of the examined cases. Regarding the Ki-67 positive rate in the inner nodule, the Ki-67 positive rate in the p53 protein positive cases was significantly higher than that in the negative cases (30.3 +/- 15.4 vs. 11.9 +/- 9.2; p < 0.05). However, the TUNEL labeling index was not affected by the expression of those proteins.


CONCLUSIONS
This study suggested that tumor progression depends on a disturbance in the cell kinetic balance caused not by a decrease in the absolute amount of cell loss but in the chaotic balance between cell loss and cell proliferation.
Yamamoto
K
K
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Takenaka
K
K
Kajiyama
K
K
Shimada
M
M
Shirabe
K
K
Taketomi
A
A
Maeda
T
T
Sugimachi
K
K
D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology*; D008940:Mitotic Index; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor