Parathyroid atypical adenomas: mutational screening of CDC73/HRPT2 gene
E. Pardi, S. Borsari, C. Banti, F. Saponaro, L. Torregrossa, C. Marcocci & F. Cetani
Atypical parathyroid adenomas represent a subset of tumors with histological features worrisome for carcinoma (PC), such as trabecular growth, fibrous bands and increased mitotic activity without unequivocal criteria of malignancy (local recurrence and/or metastasis). The question of whether these lesions might represent an anticipation of an aggressive clinical behavior that overtime may acquire the full blown features of malignancy remains to be established.
CDC73/HRPT2 tumor suppressor gene mutations have been reported in up to 80% of sporadic PC, mainly associated with reduced expression or loss of its encoded protein, parafibromin. With the exceptions of some studies on parafibromin expression, there are no genetic studies of HRPT2 gene on atypical adenomas.
We collected 15 parathyroid atypical adenomas from patients with sporadic primary hyperparathyroidism (PHPT), obtained at the time of surgery or retrieved from paraffin embedded sections. All but one patients, 8 males and 7 females, with a mean age at diagnosis of 47 years (range 1668 yrs), were submitted to a single parathyroidectomy. Familial history of PHPT was negative in all patients. Follow-up after surgery ranged from 6 months to 9 years.Thirteen patients were cured by surgery, and two had persistent PHPT.
All specimens were screened for HRPT2 mutations. The entire coding region of the gene and splice sites were sequenced with a BigDye chemistry.
A heterozygous mutation in the donor splice site of intron 1 (c.131G>T) was identified in one adenoma. Unexpectedly, this mutation was a germline mutation, carried by the younger patient of our series. The mutation was also found in the patients healthy father. The remaining tumors were negative.
Our results suggest that the involvement of HRPT2 gene in parathyroid atypical adenoma is rare. However, HRPT2 gene screening can be suggested in young patients with single atypical parathyroid adenoma.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.