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Open access

Irfan Vardarli, Manuel Weber, Frank Weidemann, Dagmar Fuehrer, Ken Herrmann, and Rainer Görges

Objective: The usefulness of routine calcitonin measurement for early detection of medullary thyroid carcinoma (MTC) in patients with nodular thyroid disease (NTD) has been investigated in various studies. Recently, a Cochrane review has been published on this issue, but a meta-analysis is lacking yet. Therefore, we performed this meta-analysis.

Methods: We performed an electronic search using PubMed/Medline, Embase and the Cochrane Library. Studies assessing the diagnostic accuracy of routine calcitonin measurement for detecting MTC in patients with NDT were selected. Statistics were performed by using Stata software, risk of bias was assessed using Review Manager version 5.3.

Results: 17 studies, involving 74,407 patients were included in the study. Meta-analysis, using the bivariate random effects model and the hierarchical summary receiver operating characteristic (HSROC) curve revealed the following pooled estimates: sensitivity 0.99 (95% CI, 0.81-1.00), specificity 0.99 (95% CI, 0.97-0.99), positive likelihood ratio (L+) 72.4 (95% CI, 32.3-162.1), and negative likelihood ratio (L-) 0.01 (95% CI, 0.00-0.23). Meta-regression analysis showed that the threshold of basal calcitonin is an independent factor, but in particular performing of stimulation test is not an independent factor.

Conclusions: We showed that routine basal serum calcitonin measurement in the management of patients with thyroid nodules is valuable for the detection of MTC. However, the published cut-off values should be considered and, if applicable, the patients monitored in a wait-and-see strategy by experienced physicians to avoid overtreatment.

Open access

Marc Ingenwerth, Tim Brandenburg, Dagmar Führer-Sakel, Moritz Goetz, Frank Weber, Henning Dralle, Hans-Ulrich Schildhaus, Kurt Werner Schmid, and Sarah Theurer

Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbour somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Since stromal desmoplasia in sporadic MTC has been identified as a reliable predictor of aggressive behaviour and development of lymph node metastases, a possible correlation of DLL3 expression with the presence of stromal desmoplasia was of particular interest. 59 paraffin-embedded samples of sporadic MTC with (44 cases) and without (15 cases) stromal desmoplasia and known lymph node status were included. DLL3 expression was determined by immunohistochemistry; no expression (0%), low expression (1-49%) and high expression (≥ 50 %) were correlated with clinicopathological data. The proportion of DLL3 positivity was significantly correlated with both stromal desmoplasia (p < 0.0001) and lymph node metastases (p < 0.0001). MTC without stromal desmoplasia consistently lack DLL3 expression. This is the first study to focus on MTC regarding DLL3 expression and the relationship to various factors. Our results demonstrate that expression of DLL3 in MTC represents a reliable surrogate marker for stromal desmoplasia and lymph node metastases and might be an indicator for aggressive clinical behaviour. DLL3 expression in >50% of tumor cells virtually excludes MTC without stromal desmoplasia.DLL3 was discussed as a potential therapeutic target in malignant tumors of other locations with positive immunohistochemical reaction and might therefore be a new therapeutic option in MTC, as well.