'de novo'
carcinogenesis has been advocated besides '
adenoma carcinoma sequence' as another dominant pathway leading to
colorectal carcinoma. Our recent study has demonstrated that the distribution of brain (fetal)-type
glycogen phosphorylase (BGP) positive foci (BGP foci) has a close relationship with the location of 'de novo'
carcinoma. The aims of the present study are to investigate genetic alteration in the BGP foci and to characterize them in the 'de novo'
carcinogenesis. 17
colorectal carcinomas without any
adenoma component expressing both immunoreactive p53 and BGP
protein were selected from 96 resected specimens from our previous study. Further investigations to examine the
proliferating cell nuclear antigen (
PCNA)-labelling index, and the p53 and the
codon 12 of K-ras mutation using the polymerase chain reaction-single strand conformation polymorphism were performed in the BGP foci, BGP negative mucosa and
carcinoma. The BGP foci were observed sporadically in the transitional mucosa adjacent to the
carcinoma in all cases. The
PCNA labelling index in the BGP foci was significantly higher than that in the BGP negative mucosa (P< 0.001). p53 mutations were observed in 8
carcinomas, but no K-ras mutation was detected. Interestingly, although none of the overexpressions of p53
protein was detected immunohistochemically in the BGP positive foci, the p53 gene frequently (41.2% of the BGP foci tested) mutated in spite of no K-ras mutation. The present study demonstrates potentially premalignant foci in the colorectal transitional mucosa with frequent p53 gene mutation. It is suggested that BGP foci are promising candidates for the further investigation of 'de novo' colorectal
carcinogenesis.