Endocrine Abstracts

Parathyroid carcinomas (PCas) are rare endocrine malignant neoplasia characterized by an abnormal PTH secretion and, consequently, severe and uncontrolled hypercalcemia. Clinically, the preoperative diagnosis can be misleading, because PCas share some molecular and clinical similarities with benign lesions and are often indolent. The histological diagnosis of carcinoma is achieved based on the presence of mitotic nuclear figures, capsular invasion, parenchyma infiltration, vascular invasion and, less frequently, distant metastasis. Moreover, there is no molecular biomarker that could support PCas diagnosis. LncRNAs are an important class of epigenetic regulators involved in both physiological processes and cancer development. Preliminary evidence suggested that lncRNAs could act as accurate prognostic and diagnostic biomarkers. Recently, we identified a long non-coding RNAs (lncRNAs) signature able to distinguish PCas from benign parathyroid adenomas (PAds) and normal parathyroid glands. Particularly, the lncRNA BCYRN1/BC200 emerged as an interesting candidate biomarker for the diagnosis of PCas. In gastric, colorectal and breast cancers BC200 expression is dramatically increased and positively correlates with distant metastasis, tumor size and clinical stage. We previously reported that BC200 is overexpressed in PCas tissues harboring CDC73 gene inactivating mutations. Here, we found that BC200 is also upregulated in metastatic PCas (n=4) compared to the non-metastatic (n=9) parathyroid carcinomas. Then, we tested the hypothesis that circulating BC200 expression may provide a clinical and non-invasive biomarker to distinguish PCas from PAds. To this end, we analyzed circulating BC200 expression levels in serum samples from patients affected with PCas (n=4) and PAds (n=22) through digital PCR. All samples were collected prior parathyroidectomy. Our results show that BC200 counts are higher in the serum of patients affected with PCas compared to those detected in serum of patients harboring PAds. Moreover, serological BC200 counts positively correlate with circulating PTH and total calcium levels and age at diagnosis in PAds. Lastly, we analyzed circulating BC200 expression in the serum of 3 PCa patients before and after parathyroidectomy. BC200 counts are reduced in all 3 postoperative PCas serum samples compared to the preoperative specimens, suggesting its potential use also as a useful non-invasive biomarker in the clinical follow-up of PCa patients. These findings extend the knowledge on BC200 in parathyroid tumors, supporting its role as a novel tissue and circulating biomarker for PCas diagnosis.