Endocrine Abstracts

Introduction: Medullary thyroid carcinoma (MTC) accounts for 3.5-5% of thyroid cancers. The biochemical diagnosis of MTC is based on the determination of concentration of a sensitive and specific biomarker - calcitonin (CT) as well as CEA and procalcitonin (PCT). Neuroendocrine cells have the ability to produce various proteins and neuropeptides (e.g. granin proteins and INSM-1), which are secreted into the circulation with calcitonin and can be measured in the blood as so-called circulating tumor markers.

Purpose: The aim of the study was to assess the usefulness of determining levels of selected granin family proteins and INSM-1 in the diagnosis of patients with medullary thyroid cancer.

Material and methods: 34 patients with medullary thyroid carcinoma (MTC) were enrolled in the study. Patients were divided into 2 groups:

1. MTC – active form (7 patients with newly diagnosed MTC and 8 patients with distant metastases (4-15 years after thyroidectomy),

2. MTC – stable form, with no recurrence nor metastases (n=19).

Forty healthy individuals were the control group. The following levels were determined in all patients: calcitonin, procalcitonin, CEA, INSM-1, proSAAS, chromogranin B (CgB), chromogranin A (CgA) and derivates peptides: Pancreastatin/chromogranin A (250-301), Serpinin/prepro-chromogranin A (429-454), WE-14/prepro-chromogranin A (342-355) and Catestatin.

Results: In MTC-active patients levels of: CT, CEA, PCT, INSM-1, WE-14, Catestanin and Serpinin were significantly different vs. control group, with higher level in MTC patients. No significant difference was confirmed for CgA, CgB, pro-SAAS and Pancreastatin between MTC-active and the control group. For MTC-stable patients, only CEA, INSM-1 and Serpinin levels were significantly higher compared to the control group. In the group of patients with the active form of MTC, the following indicators of the diagnostic evaluation of the analyzed biomarkers were obtained: CT: 93% sensitivity and 100% specificity (AUC 0.968), PCT: 100% sensitivity and specificity, INSM-1: 100% sensitivity and 95% specificity (AUC 0.997), WE-14: 86.7% sensitivity and 87.5% specificity (AUC 0.922), Catestatin: 80% sensitivity and 85% specificity (AUC 0.899), Serpinin: 53% sensitivity and 95% specificity (AUC 0.764). In the group of MTC-stable form patients, the highest diagnostic usefulness was the determination of INSM-1 level: 57.9% sensitivity and 82.5% specificity (AUC 0.720) and Serpinin: 47.4% sensitivity and 90% specificity (AUC 0.737).

Conclsion: In patients with active MTC, the greatest diagnostic usefulness was found for the determination of CT, PCT and CEA levels as well as of new biomarkers: INSM-1 and selected peptides from the granin family: WE-14, Catestatin and Serpinin.