Promoter Methylation and Parathyroid Carcinoma.

Context: Parathyroid carcinoma (PC) is extremely rare. Prognosis is poor, with no known evidence-based systemic therapies. We previously reported complete remission in a patient with metastasized parathyroid carcinoma and high tumor promoter methylation status who was treated with temozolomide.

Objective: To study promoter methylation status in an additional set of aggressive parathyroid tumors.

Design/setting: The study included 12 patients: 7 with sporadic and 5 with familial primary hyperparathyroidism (two of the latter carried a gross deletion). Patient 9 is the previously described patient with PC and high methylation status. Her daughter (patient 12) had surgery for severe primary hyperparathyroidism due to atypical parathyroid adenoma during pregnancy. Eleven patients thus had PC and one had atypical parathyroid adenoma. promoter methylation status was determined from DNA extracted from primary (n = 10) or metastatic (n = 2) tumors. A mean methylation level >20% was considered high. Patient 11 had metastatic PC and received temozolomide cycles.

Results: Only the previously published patient (patient 9) had high tumor promoter methylation status. This was not a characteristic of the atypical parathyroid adenoma of the daughter (patient 12). Patient 11 ( intragenic deletion) has disseminated PC, low promoter methylation, and stable disease on follow-up after temozolomide treatment.

Conclusion: High promoter methylation status seems rare in PC. However, as demonstrated in other neuroendocrine tumors, some patients with disseminated PC might benefit from temozolomide. Demonstration of high methylation status could be a predictor of positive response to temozolomide treatment.