MON-851 - WT1 as A Novel Immunohistochemical Marker for Parathyroid Cancer

Background: Parathyroid carcinoma (PC) is a rare malignancy associated with poor clinical outcomes. Currently, there is a shortage of reliable immunohistochemical (IHC) markers for PC. WT1 is known to directly repress CDC73 and induce MYC and BCL-2, thereby promoting cell proliferation and tumorigenesis. In this study, we aimed to validate the clinical utility of WT1 as an IHC marker for PC.

Methods: Patients diagnosed with PC at Severance Hospital between 2015 and 2025 were enrolled. Formalin-fixed, paraffin-embedded tissue sections were subjected to IHC staining for WT1. Positivity was defined as moderate-to-strong intensity in >5% of tumor cells. Data on parafibromin staining and germline CDC73 mutation status were collected via electronic medical record review. To evaluate the diagnostic performance of WT1, a separate cohort of 180 patients with parathyroid adenoma was utilized.

Results: A total of 21 patients with PC were included (median age: 45 years; 57.1% female). Parafibromin loss and WT1 positivity were observed in 38.1% (8/21) and 47.6% (10/21) of patients, respectively. WT1 IHC staining demonstrated a sensitivity of 47.6% and a high specificity of 99.4% for differentiating PC from adenoma. Notably, WT1 positivity was significantly associated with germline CDC73 mutations (60.0% vs. 9.1%; p = 0.024), with an odds ratio of 12.90 (95% CI: 1.07–752.55). In contrast, parafibromin loss did not show a statistically significant association with germline CDC73 mutations (50.0% vs. 23.1%; p = 0.346, OR = 3.13).

Conclusion: WT1 expression is a highly specific marker for PC and is significantly associated with CDC73 mutations. While its sensitivity is modest, WT1 positivity serves as a strong indicator of both malignancy and CDC73 alterations, making it a valuable tool in the diagnosis of PCs.

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