Cancer-Derived Immunoglobulin G: A Novel Marker for Differential Diagnosis and Relapse Prediction in Parathyroid Carcinoma

Ming Cui; Ya Hu; Bang Zheng; Shenghua Zhang; Xiang Zhang; Mengyi Wang; Xiao-Yan Qiu; Quan Liao; Yu-Pei Zhao


Clin Endocrinol. 2020;92(5):461-467. 

In This Article

Abstract and Introduction


Objective: A differential diagnosis between malignant and benign parathyroid lesions is difficult due to their overlapping clinicopathological characteristics. As such, molecular markers are urgently needed. Cancer-derived immunoglobulin G (CIgG) is a novel molecule playing important roles in carcinogenesis. The present study aimed to investigate the clinical significance of CIgG in parathyroid neoplasms.

Patients: Fifty patients with parathyroid carcinoma (PC), 50 patients with parathyroid adenoma (PA) and 9 patients with parathyroid hyperplasia (PH) were retrospectively enrolled in the current study.

Measurements: Immunohistochemistry was used to assess CIgG expression in these patients. The performance of CIgG expression in the differential diagnosis between parathyroid lesions was assessed by receiver operating characteristic (ROC) curves. The associations between CIgG expression and clinical outcomes were also analysed by Kaplan-Meier survival curves and Cox proportional hazards models.

Results: The expression level of CIgG was significantly higher in PC patients than in PA or PH patients (P < .001). CIgG expression discriminated PC from PA or PH, with an area under the ROC curve of 0.84 (76% sensitivity and 88% specificity). High CIgG expression was significantly associated with worse disease-free survival (DFS) in PC patients (P = .018) and was validated as an independent risk factor for DFS in the multivariable Cox regression analysis (P = .002).

Conclusions: The ability of CIgG expression both in the differential diagnosis between malignant and benign parathyroid lesions and in the prognosis prediction for PC was shown in the present study. CIgG might be used as a novel biomarker of parathyroid lesions in future clinical practice.


Parathyroid carcinoma (PC) is a rare endocrine malignancy with increasing incidence in recent years.[1] PC accounts for less than 1% of cases of primary hyperparathyroidism (PHPT) in western countries and approximately 5% of cases of PHPT in China.[2,3] In contrast to benign parathyroid lesions such as parathyroid adenoma (PA) or parathyroid hyperplasia (PH), PC presents a poor prognosis for patients due to its malignant biological behaviour accompanied by severe clinical symptoms. The 5- and 10-year overall survival (OS) rates for PC patients are reported to be 82.3% and 66%, respectively.[4] An early and accurate diagnosis is critical to improve the prognosis of this malignancy. A differential diagnosis between PC and other benign parathyroid lesions remains challenging due to their overlapping clinical presentations and pathological features, especially at an early stage. To overcome this dilemma, molecular markers such as parafibromin, Ki-67, Galectin-3 and some noncoding RNAs have been studied previously.[5–7] However, powerful differential markers remain limited.

Immunoglobulins (Igs) are a family of immune molecules that play essential roles in immunity responses. In the last decade, Ig has been innovatively detected in cancer tissues and was validated to be expressed by cancer cells themselves; it was thus named cancer-derived immunoglobulin.[8–12] Related studies have revealed that cancer-derived immunoglobulin G (CIgG) participates in maintaining the malignant behaviours of cancer cells by displaying growth-factor–like activity.[8,13,14] With the application of the monoclonal antibody RP215, which can specifically recognize a glycosylated epitope of the CIgG heavy chain but not IgG derived from B cells, it becomes practical to detect the expression of CIgG in cancer tissues.[14,15] Further studies showed that CIgG recognized by the RP215 antibody was specifically expressed in cancer cells, and its expression indicated a poor prognosis in patients with cancer.[16,17] As such, CIgG has presented promising roles in the diagnosis and prognosis prediction of cancer.

The aim of the present study was to detect whether CIgG was expressed in parathyroid neoplasms and to evaluate its significance in differential diagnosis and prognosis prediction for parathyroid neoplasms. In this study, we explored the expression of CIgG in a series of patients with benign and malignant parathyroid lesions. The prognostic value of CIgG was investigated in the cohort of PC patients.