Relationship between p53 overexpression and the proliferative activity in hepatocellular carcinoma

Relationship between p53 protein overexpression and clinicopathological fin dings and the proliferative activity was studied in 50 cases of hepatocellu lar carcinoma (34 biopsy and 16 surgically resected cases) using immunohist ochemistry. Overexpression of p53 was observed in 26.5% of biopsy cases and 31.3% of surgically resected cases. Investigation of the relationship betw een the p53-positive rate and the clinical stage of HCC showed that it was significantly higher in Stage IV (the most advanced cancer; 54.5%) than in Stage I/II/III (13.0%) (p<0.05). Examination of the relationship between th e p53-positive rate and tumor differentiation in the biopsy cases showed th at p53 was positive in 9.1% of well differentiated carcinomas, 21.4% of mod erately differentiated carcinomas, and 55.6% of poorly differentiated carci nomas, indicating that p53 positivity increased as tumors became less diffe rentiated. The p53-positive rate of poorly differentiated carcinoma (55.6%) was significantly higher than that of well and moderately differentiated c arcinoma (16.0%) (p<0.05). In the surgically resected cases, p53 overexpres sion tended to be more frequent in the less differentiated parts of each tu mor nodule. In cases with nodule in nodule pattern of HCC, the p53-positive rate was different among nodules with the same level of differentiation. E xamination of tumor cell proliferative activity using the proliferating cel l nuclear antigen L.I. showed that this indicator was significantly higher in the p53-positive tumors than in the p53-negative tumors (52.7+/-32.4% vs . 32.4+/-15.3%: p<0.05). These results suggest that p53 overexpression may be involved in determining the dedifferentiation and the proliferative acti vity of HCC. Examination of the surgically resected cases confirmed that p5 3 overexpression became heterogeneous during the multistep carcinogenesis a nd growth process of HCC, which is considered to develop from a single cell . This finding suggests that p53 overexpression may be involved in tumor pr ogression.