P53 mutations in human adrenocortical neoplasms

The mechanisms of tumorigenesis of adrenocortical neoplasms have
not been elucidated as yet. However, loss of heterozygosity at
chromosomal locus 17p has been consistently observed in
adrenocortical cancer. p53 is a recessive tumor suppressor gene
located on chromosome 17p. Mutations in the p53 gene play an
important role in the tumorigenesis of diverse types of human
neoplasms including breast and colon cancers. More than 90% of all
mutations discovered in such tumors have been detected in 4 hot
spot areas that lie between exons 5 and 8. In contrast to wild-type
p53, mutant p53 accumulates intracellularly and can be easily
detected by immunohistochemistry. We therefore investigated the
frequency of p53 mutations in human adrenocortical neoplasms using
molecular biology and immunohistochemistry techniques. Five
patients with adrenocortical adenomas (5 female; ages 39-72 yr), 11
patients with adrenocortical carcinomas (8 female, 3 male; ages 15-
50 yr), and two adrenocortical tumor cell lines were studied. After
DNA extraction from frozen tumor tissue or paraffin-embedded
material, exons 5 through 8 were amplified using the polymerase
chain reaction and directly sequenced by the dideoxy termination
method. Immunohistochemistry was performed on paraffin-embedded
tumor specimens obtained during adrenalectomy using a monoclonal
antibody reacting with both wild-type and mutant p53. Prevalence of
mutations was adenomas, 0/5, carcinomas, 3/11, and adrenocortical
cell lines, 2/2. Single point mutations were detected in 3 cases
(exons 5, 6, and 7, respectively), and rearrangements of exon 7/8
and 8 were found in 2 cases. Immunohistochemistry detected strong
nuclear and/or cytoplasmic p53 immunoreactivity in all
adrenocortical carcinomas with point mutations of the p53 gene but
not in adenomas and carcinomas with the wild-type sequence or with
deletion/rearrangement of the p53 gene. We conclude that p53 plays
a role in the tumorigenesis of adrenocortical carcinomas but is of
less importance to benign adenomas.