DNA sequencing of the removed adenoma confirmed a hemizygous nonsense variant in the CDC73 gene in a mosaic manner, which was potentially involved in parathyroid tumorigenesis as the "second hit."
Male patients with high-proliferative tumors were overrepresented among cases with aberrant parafibromin immunohistochemistry, and carcinomas more frequently harbored parafibromin aberrancies than atypical adenomas and adenomas (p < 0.001).
A previously unreported intragenic deletion of exons 1 to 10 of CDC73 was detected in a three-generation family with FIHP, due to adenomas, atypical adenomas, and parathyroid carcinomas.
While it is known that CDC73-mutated parathyroid tumors display specific gene expression changes compared to CDC73 wild-type cases, the molecular cytogenetic profile in CDC73-mutated cases compared to unselected adenomas (with an expected very low frequency of CDC73 mutations) remains unknown.
Loss of parafibromin immunostating showed promising results in the differential diagnosis of parathyroid carcinoma from adenoma and may also serve as a prognostic marker.
One patient, a member of a previously reported multiplex family with a germline CDC73 mutation was found to have a second adenoma after removal of an atypical adenoma.
Expression levels of nuclear parafibromin and parafibromin messenger RNA were decreased from colorectal nonneoplastic mucosa and adenomas to carcinomas (P < .05).
Furthermore, the molecular resemblance of atypical adenomas with carcinoma concerning parafibromin and APC expression indicates that atypical adenomas should be subjects to watchful follow-up.
HRPT2 and parafibromin studies improved the diagnostic accuracy in two patients with primary hyperparathyroidism (PHPT) referred to us after surgery, in whom the clinical data were at variance with the pathological diagnosis of adenoma and carcinoma, respectively.
Correlative immunohistochemical studies have revealed nuclear parafibromin immunoreactivity in adenomas but absence or partial loss of staining in PTCAs.
Our study shows that different somatic genetic events at the HRPT2 locus are responsible for the asynchronous occurrence of multiple adenomas in a patient carrying an HRPT2 germline mutation.
No intragenic HRPT2 mutations were detected, strengthening the degree of specificity of HRPT2 mutation as a feature of sporadic parathyroid carcinoma as opposed to sporadic adenomas.
Furthermore, our findings likely preclude an adenoma to carcinoma progression model for parathyroid tumorigenesis outside of the presence of either a germ-line or somatic HRPT2 mutation.
The similar loss of parafibromin immunoreactivity in HPT-JT syndrome-related adenomas suggests that this is a pivotal step in parathyroid tumorigenesis.