唾液腺癌におけるp53遺伝子変異と核DNA解析およびAgNOR法による腫瘍増殖能の検討

抄録

Recent studies have shown that inactivation of tumor suppressor p53 gene is a key point in the development of human carcinomas and that normal p53 protein acts as a "molecular policeman" monitoring the integrity of the genome. In the present study, a series of 22 primary human salivary gland carcinomas were examined for alterations and expression of the p53 gene by a combined molecular and immunohistochemical approach, polymerase chain reaction single-strand conforma tion polymorphism (PCR-SSCP), direct gene sequencing and p53 protein immunostaining. In addition, in order to identify correlations between p53 abnormalities and genetic instability, DNA aneuploidy and tumor growth characteristics were analyzed by cytofluorometry and the AgNOR technique. Seven of the 22 cases displayed nuclear p53 overexpression as revealed by immuno staining with p53 monoclonal antibody (Do-7), and 2 of these 7 cases were associated with the presence of point mutations [codon 140: ACC (Thr)→ATC (Ile), codon 175: CGC (Arg)→CAC (His)] of the p53 gene. Twelve of the 22 cases were aneuploid on the DNA histogram, and this phenomenon was statistically correlated with the 7 cases exhibiting p53 nuclear accumulation. AgNOR staining, on the other hand, was not statistically correlated with p53 abnormalities. These findings support the view that abnormal nuclear accumulation of the p53 protein is correlated with genetic instability of human salivary gland carcinoma cells.