Utility of proGRP as a tumor marker in the medullary thyroid carcinoma

Abstract

Background:Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor caused by a malignant transformation in the parafollicular C-cells of the thyroid, where calcitonin (CT) is released. Nowadays the main tumor markers (TM) used in the diagnosis and follow-up of MTC patients are CT and carcinoembryonic antigen (CEA). Nonetheless, progastrin releasing peptide (proGRP) has been recently proposed as a TM useful in the MTC. Our aims were to investigate the release of proGRP in thyroid tumors, its role in the assessment of advanced MTC and its utility in the differential diagnosis between MTC and non-MTC thyroid tumors.Methods:Serum samples from 22 patients with MTC and 16 with non-MTC were collected. Patients were classified into advanced cancer or no evidence of disease (NED). ProGRP was performed by Architect (Abbot Diagnostics), CT by Liaison (Diasorin) and CEA by Cobas E601(Roche Diagnostics).Results:ProGRP median concentration in advanced MTC was significantly higher (1398.4 pg/mL) when compared with non-MTC, either in advanced disease (24.9 pg/mL) or NED (14.6 pg/mL). In non-MTC patients, proGRP median concentration was below its cutoff level (50 pg/mL). Similar to CT, proGRP was able to detect 88.9% of MTC patients, but with a slightly lower specificity of 76.9%. Using proGRP together with CT the sensitivity increased to 100%.Conclusions:The low prevalence of this malignancy strongly recommends further collaborative studies, mainly focused on monitoring proGRP during tyrosine kinase inhibitors treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and CEA.

A Nationwide Study of Multiple Endocrine Neoplasia Type 2A in Norway: Predictive and Prognostic Factors for the Clinical Course of Medullary Thyroid Carcinoma

“…Other secretory biomarkers as CEA, chromogranin A (CgA) and pro gastrin-releasing peptide (proGRP) increase at MTC and might be useful tumor markers, although CgA first increase in aggressive MTC (176)(177)(178)(179)(180). CEA is an integral part of the cell membrane of MTC tumor cells, from where it can be released and serve as a tumor marker (149,181).…”

“…In contrast to serum calcitonin, which has to be analyzed immediately or transported frozen to the laboratory, proGRP is stable in blood where it can be measured (183,184). The ProGRP serum level may also be useful, in addition to calcitonin, in diagnosing and follow-up of MTC, and can be analyzed in FNB wash out (179,180 (189,190).…”

Elevated basal serum levels of calcitonin and simultaneous surgery of MEN2A-specific tumors

“…Regarding proGRP, it was widely distributed in neuroendocrine cells of non-gastric antrum, nerve bers, brain and lung [10,12]. Accumulating evidence suggested that proGRP levels also had signi cant correlation with MTC but not with non-MTC (follicular thyroid carcinoma [FTC] and papillary thyroid carcinoma [PTC]) [10,11,13]. Ide et al [10] reported that proGRP levels above the cut-off value, respectively, accounted for 80% ( [11] analyzed the sensitivity of Ctn, CEA and proGRP, individually and in combination.…”

“…Accumulating evidence suggested that proGRP levels also had signi cant correlation with MTC but not with non-MTC (follicular thyroid carcinoma [FTC] and papillary thyroid carcinoma [PTC]) [10,11,13]. Ide et al [10] reported that proGRP levels above the cut-off value, respectively, accounted for 80% ( [11] analyzed the sensitivity of Ctn, CEA and proGRP, individually and in combination. The results showed: (i) Similar to Ctn (88.9%), sensitivity related predominance in terms of proGRP was observed as indicated by the CEA-to-proGRP ratio of approximately 1:1.4 (62.5%:88.9%); (ii) If CEA or proGRP is intended to be served as a complement to Ctn, respectively, the ratio of sensitivity was approximately 1:1.12 (88.9%:100%).…”

Novel Markers for Early Diagnosis and Prognostic Classification in Medullary Thyroid Carcinoma

“…In patients with residual, metastatic, progressive disease, classical cytotoxic drugs were proven to be inefficient. Drugs that inhibit different kinases, including RET, such as sorafenib, sunitinib, motesanib, cabozantinib and vandetanib, appear to be a key therapy for these patients (11).…”