|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1998 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1997 : ¥1,900,000 (Direct Cost : ¥1,900,000)
To explore the clinical significance of p53 in the pathogenesis of adrenal neoplasms, we investigated the incidence of p53 gene mutations in functioning human adrenal tumors using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to screen p53 exons 4 to 9. We examined 29 adrenocortical adenomas (primary aldosteronism, n=17 ; Cushing's syndrome, n=12, all benign), and 33 pheochromocytoma (benign solitary, n=18 ; benign multiple, n=5 ; malignant, n=1O) in Japanese and Chinese patients. PCR-SSCP did not show any abnormal band-shifts in any of the adrenocortical adenoma and benign solitary pheochromocytoma tissues. In contrast, six pheochromocytoma tissues (two cases benign multiple, four cases malignant) showed PCR-SSCP band-shifts. Subsequent DNA sequencing analysis of the shifted bands demonstrated that three cases contained point mutations within intronic regions, one case a silent mutation in exon 8, and three cases contained missense mutations (one case each in exons 5, 6 and 9). Immunohistochemical staining demonstrated that two of three cases with missense mutations and one case with an intronic mutation over-expressed p53 protein in tumor cell nuclei. As p21/WAF-l/CIP-1, a downstream mediator of p53, was expressed only in scattered pheocromocytoma tumor cell nuclei, we observed no association between p21/WAF-1/CIP-1 expression and mutation or over-expression of p53. The relatively high incidence of p53 gene mutations in multiple and malignant pheochromocytoma, but not in benign solitary cases, suggests that p53 mutation could play an important role in the pathogenesis of multiple and/or malignant pheochromocytoma. However, p53 mutations do not appear to play a role in the tumorgenesis of functioning adrenocortical adenoma.