Prognostic role of parafibromin staining and CDC73 mutation in patients with parathyroid carcinoma: A systematic review and meta‐analysis based on individual patient data

Abstract

Background and Objective Parathyroid carcinoma (PC) is a rare malignant neoplasm with a relatively poor prognosis. The loss of parafibromin expression or the presence of CDC73 mutation has been found to be remarkably associated with malignancy in parathyroid tumours. However, the prognostic role of them in PC has not yet been shown due to sampling limitations. We conducted a systematic review and meta‐analysis based on individual patient data to clarify the performance of parafibromin immunohistochemical staining and CDC73 gene sequencing in predicting outcomes for patients PC. Methods Published studies from PubMed/MEDLINE, EMBASE, Cochrane and Scopus Databases were searched using the terms ‘parafibromin’, ‘CDC73’, ‘HRPT2’ and ‘parathyroid’ to identify eligible studies. From the included studies, the survival data of patients with PC were extracted, and a Cox proportional hazards model was used to assess hazard ratio (HR) for disease‐free survival (DFS) and overall survival (OS). Results A total of 193 patients from 9 studies were included in this survival analysis. Negative immunohistochemical staining of parafibromin was shown to be a risk factor for recurrence/metastasis (HR 2.73, P = .002) and death (HR 2.54, P = .004). Patient age ≥ 50 years was significantly related to lower OS (HR 2.37, P = .004) but not to DFS. CDC73 mutation was not statistically related to DFS or OS. Conclusions Negative parafibromin staining indicated a higher risk of recurrence/metastasis and mortality. The immunohistochemical staining of parafibromin seems to be more promising in predicting outcomes for patients with PC than the sequencing of CDC73.

Parathyroid carcinoma: Single centre experience

“…Some data suggests that CDC73/HRPT2 mutation may be a marker of poor prognosis and increased risk of recurrence 33 . In our study, recurrence during follow‐up was observed in 60% (3/5) of patients with CDC73/HRTP2 mutation and 43% (3/7) of analysed patients without identifiable mutation.…”

Genomics and Epigenomics in Parathyroid Neoplasia: from Bench to Surgical Pathology Practice

“…As parafibromin is a predominant nuclear protein, loss of nuclear immunoreactivity is considered pathognomonic for an underlying inactivating CDC73 mutation. As most CDC73 mutations, be it germline or somatic, are either deleterious, located in early exons (causing premature termination) or missense alterations in important regulatory regions (such as the nuclear localization regions), mutated parafibromin is usually unable to reach its nuclear localization [97,151,152]. Most studies therefore seem to agree that almost all parathyroid tumors with wildtype CDC73 sequence display a diffuse positive parafibromin stain (Fig.…”

Parathyroid Carcinoma All-In-One, a Rare Life-Threatening Case With Multiple Systemic Manifestations: Case Report and Review of the Literature

“…Although in the reported case it was not assessed, parafibromin staining may play a prognostic role in patients with PC. Indeed, as widely described by a recent review ( 19 ), negative immunohistochemical staining of parafibromin seems to be promising in predicting outcomes for patients with PC, indicating a higher risk of recurrence/metastasis and mortality. Recent findings showed that cancer‐derived immunoglobulin G (CIgG) is expressed in parathyroid neoplasms and highly expressed in PC.…”