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 tumours 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 phaeochromocytomas (benign solitary, n=18; benign multiple, n=5; malignant, n=10) in Japanese and Chinese patients. PCR-SSCP did not show any abnormal band-shifts in any of the adrenocortical adenoma and benign solitary phaeochromocytoma tissues. In contrast, six phaeochromocytoma tissues (two cases benign multiple, four cases malignant) showed PCR-SSCP band-shifts. Subsequent DNA sequencing analysis of the shifted bands revealed six cases with nine mutations or intronic sequence alterations: three cases contained sequence alterations within intronic regions, three cases with silent mutation (sequence alteration in codon without amino acid alteration), 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 sequence alteration over-expressed p53 protein in tumour cell nuclei. We observed no association between p53 gene mutation and p21/WAF1/Cip-1 expression. The relatively high incidence of p53 gene mutations or intronic sequence alteration in multiple and malignant phaeochromocytomas, but not in benign solitary cases, suggests that p53 mutation could play some role in the pathogenesis of multiple and/or malignant phaeochromocytomas.

This article has been cited by other articles:

				T. E. Rohan, S.-Q. Li, R. Hartwick, and R. A. Kandel p53 Alterations and Protein Accumulation in Benign Breast Tissue and Breast Cancer Risk: A Cohort Study. Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1316 - 1323. [Abstract] [Full Text] [PDF]

				S. J. Marx and W. F. Simonds Hereditary Hormone Excess: Genes, Molecular Pathways, and Syndromes Endocr. Rev., August 1, 2005; 26(5): 615 - 661. [Abstract] [Full Text] [PDF]

				C. A. Koch, K. Pacak, and G. P. Chrousos The Molecular Pathogenesis of Hereditary and Sporadic Adrenocortical and Adrenomedullary Tumors J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5367 - 5384. [Abstract] [Full Text] [PDF]

				K Y Lam, C Y Lo, N M S Wat, J M Luk, and K S L Lam The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas J. Clin. Pathol., June 1, 2001; 54(6): 443 - 448. [Abstract] [Full Text] [PDF]

				K. Salmenkivi, J. Arola, R. Voutilainen, V. Ilvesmäki, C. Haglund, A. I. Kahri, P. Heikkilä, and J. Liu Inhibin/Activin {beta}B-Subunit Expression in Pheochromocytomas Favors Benign Diagnosis J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2231 - 2235. [Abstract] [Full Text]