The Consistency of CDC73 Mutation and Parafibromin Staining Loss in Parathyroid Neoplasm: A Systematic Review.

Background: Primary hyperparathyroidism (pHPT) caused by parathyroid neoplasm is a common endocrine disorder. Nuclear staining loss of parafibromin, encoded by the CDC73 gene, has been shown to be closely related to parathyroid malignancy and poor prognosis. Although previous studies have found that parafibromin staining loss is not always consistent with CDC73 mutation, the reasons are still unknown. Methods: Published studies from the PubMed database were searched using the terms "parafibromin," "CDC73," "HRPT2," and "parathyroid" to identify eligible studies. Among the included studies, CDC73 mutation and parafibromin immunohistochemical (IHC) results for patients with parathyroid neoplasms were reviewed, and possible reasons for the inconsistency between the parafibromin staining loss and CDC73 mutation were explored. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 analysis protocol. Results: A total of 299 patients from 32 studies were included in the present review. Inconsistency and consistency between parafibromin staining and CDC73status was observed in 19.40% and 80.60% of patients. Patients in the inconsistency group showed higher level of serum calcium (p = 0.026). Significant difference in the inconsistency rate was found between PC (25.15%) and non-PC group (12.50%) (p < 0.001), and NGS (8.51%) and non-NGS group (21.43%) (p = 0.006) in multivariate analysis. Conclusion: The main reasons for the inconsistency were attributed to the pathological type and sequencing method. More inconsistent results were detected in the PC group and the non-NGS group.