Perineural invasion is associated with tumor spreading and an unfavorable prognosis in a variety of cancers. Recently, neural cell adhesion molecule (NCAM) has been reported to be affinitive to neural tissues, which suggests some relationship between NCAM and perineural invasion. This study was designed to elucidate the role of the expression of NCAM on the development of perineural invasion in bile duct cancer. A histopathologic study was performed on 24 patients with bile duct carcinoma who underwent resections. The overall incidence of NCAM expression in the resected specimen was 66.7% and that of perineural invasion was 87.5%. Furthermore, NCAM expression was shown to be positive in 16 (76%) out of 21 cases in whom perineural invasion was observed. A significant positive correlation was found between the expression of NCAM and perineural invasion in bile duct cancer. These results highlight an important role of NCAM in the development of perineural invasion in bile duct cancer.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin (Pr) and simvastatin (Si), suppressed 1,2-dimethylhydrazine (DMH)-induced colon cancer development in female ICR mice. All mice received an i.p. injection of 10 mg DMH/kg body wt once weekly for 15 weeks. Pr was administered at 0.01, 0.005 and 0.001% levels in drinking water, and Si at 0.01 and 0.002% levels in the diet. All animals had access to Pr or Si throughout the experiments which were terminated at weeks 25 or 30. Histologically most of the tumors were well-differentiated adenocarcinomas. The incidence of colon tumors examined at weeks 25 or 30 was reduced by 67% in the 0.01% Pr group, by 30% in the 0.005% Pr and 0.01% Si groups, and by 24% in the 0.001% Pr and 0.002% Si groups, compared with their respective controls. However, the differences did not reach statistical significance. The number of tumors per mouse was significantly reduced in all groups administered Pr and Si except the 0.001% Pr group as compared to their respective controls. The results from those three independent experiments seem to suggest that HMG-CoA reductase inhibitors may prevent colon tumorigenesis in laboratory animal model.

To clarify the role of neural cell adhesion molecule (NCAM) in perineural invasion, NCAM expression was studied by immunohistochemical staining in 26 cases with gallbladder cancer. In gallbladder cancer, the incidence of perineural invasion and that of positive NCAM expression was 42% and 31%, respectively, which are less frequent than those of bile duct cancer in our previous report. Perineural invasion was observed in 88% of the patients with positive expression of NCAM and in 22% of those with negative expression. The former is similar to that of bile duct cancer but the latter is significantly lower. Eighty percent of the cancer cells that invaded the perineural space were positive for NCAM, when the primary tumor was positive for NCAM expression. Therefore, in gallbladder cancer, positive cells in NCAM expression likely invade the perineural spaces. However, the perineural invasion of negative cells in NCAM expression is not likely to occur as compared to bile duct cancer. In conclusion, perineural invasion in gallbladder cancer is not as common as in bile duct cancer, but the role of NCAM in perineural invasion is more important in gallbladder cancer than in bile duct cancer.

In contrast to DNA-ploidy pattern, Ki-67 antigen expression showed prognostic significance in resectable DBDC. A Ki-67 positive ratio of > or =20% was associated with decreased survival time.