p53 abnormalities in human parathyroid carcinoma.
Two cell cycle regulators have been implicated in the pathogenesis of parathyroid neoplasms: rearrangement/overexpression of the PRAD1/cyclin D1 gene in parathyroid adenomas and inactivation of the retinoblastoma tumor suppressor gene in parathyroid carcinomas. We examined parathyroid tumors for evidence of molecular genetic abnormalities in another cell cycle regulator, the p53 tumor suppressor gene. Allelic loss of the p53 gene was observed in parathyroid carcinomas from 2 of 6 genetically informative patients. Moreover, 2 of 9 patients' parathyroid carcinomas had nuclear p53 protein detectable by immunohistochemical analysis, a finding that often reflects mutational stabilization of the p53 protein. Of these two p53-immunopositive carcinomas, 1 had p53 allelic loss and 1 was genetically uninformative. In contrast, none of 20 informative parathyroid adenomas exhibited p53 allelic loss; 1 of 19 adenomas had a focal region of nuclear p53 protein staining. Single strand conformation polymorphism analysis of exons 5-9 of the p53 gene did not reveal mutations in any parathyroid neoplasm, suggesting that such mutations in parathyroid tumors may lie outside of these conserved regions. The finding of both p53 allelic loss and abnormal p53 protein expression in parathyroid carcinomas implicates p53 in the pathogenesis of a subset of these tumors.
Cryns
V L
VL
Endocrine Oncology Laboratory, Massachusetts General Hospital, Boston 02114.
Rubio
M P
MP
Thor
A D
AD
Louis
D N
DN
Arnold
A
A
D000236:Adenoma / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000483:Alleles; D004273:DNA, Neoplasm / Q000737:chemistry; D005091:Exons; D017353:Gene Deletion; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53