Yamamoto K, Takenaka K, Kajiyama K, Shimada M, Shirabe K, Taketomi A, Maeda T, Sugimachi K
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hepatogastroenterology. 1999 Mar-Apr;46(26):813-9.
BACKGROUND/AIMS: 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.
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.
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.
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.
背景/目的：为了阐明肝细胞癌进展过程中细胞增殖与细胞丢失平衡的意义，对16例结节中结节型肝细胞癌手术标本进行了研究。
在16例标本中，通过Ki-67核抗原表达评估细胞增殖，并用末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法（TUNEL）检测细胞丢失。还研究了p53蛋白、bcl-2蛋白和Fas抗原的表达，以阐明它们的表达与细胞动力学之间的关系。
内结节的Ki-67标记指数高于外结节（18.9%对7.2%；p<0.05），内结节的TUNEL标记指数也高于外结节（12.8%对6.6%；p<0.05）。Ki-67标记指数从Edmondson I级到II级的增加率为3.9±3.0，从II级到III级为3.9±2.4，而TUNEL标记指数从I级到II级的增加率为2.7±0.3，从II级到III级为1.7±0.2（p<0.05）。5例在内结节边缘区观察到p53蛋白，4例发现bcl-2蛋白。然而，在所检查的病例中均未发现Fas抗原。在内结节中，p53蛋白阳性病例的Ki-67阳性率显著高于阴性病例（30.3±15.4对11.9±9.2；p<0.05）。然而，TUNEL标记指数不受这些蛋白表达的影响。
本研究表明，肿瘤进展取决于细胞动力学平衡的紊乱，这种紊乱不是由细胞丢失绝对量的减少引起的，而是由细胞丢失与细胞增殖之间的混乱平衡引起的。
