[CDC73 gene mutation and parafibromin expression status of parathyroid carcinoma in Chinese]

To explore the clinico-genetic characteristics and protein status of parathyroid carcinoma (PC) diagnosed at Peking Union Medical College Hospital from January 1980 to December 2012.

Genomic DNA was extracted from peripheral blood lymphocytes and paraffin-embedded tissue for analysis. The mutations of CDC73 gene were detected by direct sequencing. And the expression of parafibromin in tumor tissues was evaluated by immunohistochemical analysis.

Twenty-four PC patients were recruited. The mean ages at the diagnosis of PHPT and PC were 42.2 and 42.6 years respectively. The serum calcium at the diagnosis of PHPT was 3.78 mmol/L, serum phosphorus 0.65 mmol/L and the median increment of serum parathyroid hormone (PTH) level 20.0. The recurrent rate was 76.2% during a 5-year follow-up.Genetic analysis identified 11 mutations of CDC73 gene (45.8%), among which c.34_35 insCT, c.626_629 delAACA, c.260_261 delGA, c.570 delG, c.40 C>T and IVS3+1 G>A were novel mutation first identified in our cohort. Nine of them had germline mutations. All tissue samples from normal parathyroid displayed strong positive immunostaining of parafibromin. Complete (55%, 11/20) or partial (45%, 9/20) loss of parafibromin expression was observed in PC tissues. The age at the diagnosis of PHPT, serum calcium, serum phosphorus, PTH, alkaline phosphatase (ALP), bone involvement rate, kidney stone/calcification rate, recurrent rate, metastatic rate and immunostaining level showed no significant difference between the patients with and without CDC73 mutation.

In Chinese population, CDC73 mutation and complete/partial loss of immunohistochemical staining for parafibromin occur frequently in PC. Therefore it may be useful in the subset of tumors with equivocal histological examination.