Optimizing Diagnostic Accuracy of Fine Needle Aspiration Biopsy Calcitonin Measurements in Detecting Medullary Thyroid Carcinoma.

Background: The optimal cutoff value of calcitonin (Ctn) levels measured using an electrochemiluminescence immunoassay (ECLIA) obtained from the washout fluid of fine needle aspiration (FNA-Ctn) for the diagnosis of medullary thyroid carcinoma (MTC) is currently not established. We evaluated the diagnostic accuracy and clinical utility of FNA-Ctn for the diagnosis and location of MTC in patients with nodular or multinodular goiters. Methods: This was a case-control study nested on a prospective multicenter cohort of patients with nodular or multinodular goiter, normal or elevated serum Ctn, and thyroidectomy indications. Ctn and FNA-Ctn were measured using ECLIA methodology before surgery. From this nested cohort, MTC cases and controls (non-medullary pathology) were identified from the final pathological analysis. Cumulative incidence sampling of controls was randomly performed at a ratio of 1:2. Sensitivity, specificity, and area under the receiver operator curve (AUROC) were calculated for patients and the total number of thyroid nodules. Results: From 1272 patients included in the prospective cohort, 50 MTC cases and 105 controls were included. In this study, 286 thyroid nodules were evaluated (63 MTC and 223 non-MTCs). The median serum Ctn value was significantly higher in cases (525 pg/mL [interquartile range (IQR), 162.5-1.200]) than in controls (1.6 pg/mL [IQR, 0.5-5.6]; p < 0.001). The median FNA-Ctn value was significantly higher in MTC nodules (3.100 pg/mL [IQR, 450-45,200]) than in non-MTC nodules (0.5 pg/mL [IQR, 0.5-0.5]; p < 0.0001). In 11 MTC patients with multinodular goiter, the FNA-Ctn value was significantly higher in non-medullary nodules located in the same lobe where an MTC nodule was diagnosed (p = 0.0002). Overall, the FNA-Ctn AUROC was 0.99 [95% confidence interval, 0.98-1.0], and a threshold of ≥220 pg/mL showed 100% sensitivity and 98% specificity for MTC diagnosis. Conclusions: The use of FNA-Ctn measured by ECLIA showed adequate diagnostic accuracy for MTC diagnosis. Moreover, it may be clinically useful for localization in multinodular goiter when lobectomy is considered. Clinical Trial Registration: Clinicaltrials.gov NCT06067594.

Role of histamine H4 receptor in breast cancer cell proliferation.

In order to better understand the role of histamine H4 (H4R) receptor in breast cancer, we studied the receptor expression pattern, associated signal transduction pathway and biological responses, in breast cancer cell lines with different malignant characteristics. A different pattern of protein expression was observed in MDA-MB-231 compared to MCF-7 cells determined by western blot, exhibiting the presence of a diverse range of molecular weight species of the H4R. H4R agonist reduced cyclic adenosine monophosphate (cAMP) formation induced by forskolin only in MCF-7 cells. In MDA-MB-231 cells, H4R agonists significantly decreased cell proliferation, augmented the Annexin-V and TdT-mediated UTP-biotin Nick End labelling (TUNEL) positive cells and produced a 2.5-fold increase in cell senescence. In MCF-7 cells, H4R agonists inhibited proliferation by 50%, increasing the exponential doubling time. This effect was associated to an augment in Annexin-V and TUNEL positive cells, and a 2-fold increase in cell senescence. We conclude that H4R is functionally expressed in human breast cancer cell lines, exhibiting a key role in histamine-mediated biological processes such as cell proliferation, senescence and apoptosis.