calca-protein--human and Carcinoma--Neuroendocrine

An increased calcitonin serum level is suggestive of a medullary thyroid cancer (MTC), but is not pathognomonic. The possibility of false positives or other calcitonin-secreting neuroendocrine neoplasms (NENs) should be considered. Serum calcitonin levels are generally assessed by immunoradiometric and chemiluminescent assays with high sensitivity and specificity; however, slightly moderately elevated levels could be attributable to various confounding factors. Calcitonin values >100 pg/mL are strongly suspicious of malignancy, whereas in patients with moderately elevated values (10-100 pg/mL) a stimulation test may be applied to improve diagnostic accuracy. Although the standard protocol and the best gender-specific cut-offs for calcium-stimulated calcitonin are still controversial, the fold of the calcitonin increase after stimulation seems to be more reliable. Patients with MTC show stimulated calcitonin values at least three to four times higher than the basal values, whereas calcitonin-secreting NENs can be distinguished from a C-cell disease by the absence of or

Topics: Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Neuroendocrine; Diagnosis, Differential; Endocrine Gland Neoplasms; False Positive Reactions; Female; Humans; Janus Kinases; Male; Middle Aged; Reference Values; Sensitivity and Specificity; Thyroid Neoplasms

The aim of the present study was to perform a systematic review of published studies to provide a robust estimation of the use of procalcitonin (ProCT) as a diagnostic marker of medullary thyroid carcinoma (MTC), with particular focus on its specificity and negative predictive value in excluding MTC. A comprehensive computer literature search was conducted to find relevant published articles on the topic. We used a search algorithm based on a combination of the terms 'medullary,' 'thyroid,' and 'ProCT.' The search was updated until February 2015. To expand our search, references of the retrieved articles were also screened. A total of 39 articles were retrieved, of which nine original papers published from 2003 to 2014 were selected for the review. Some of these studies used ProCT in the preoperative diagnosis of MTC, whereas others measured ProCT during the follow-up of patients who had been previously treated for MTC. Other laboratory measurements were performed in some of the included studies. The results of the majority of the studies indicate that ProCT measurement appears to be a very promising and reliable serum marker for the diagnosis of MTC, and it is not inferior to calcitonin (CT). The sample handling is less laborious, and in the few CT-negative cases reviewed, the assay had even greater sensitivity. It would be worthwhile to establish cutoff levels using larger patient series, because we speculate that this assay could potentially replace CT measurement in the future.

Topics: Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Neuroendocrine; Humans; Protein Precursors; Thyroid Neoplasms; Thyroid Nodule

Early cervical lymph node (LN) metastasis is an important cause of poor survival in patients with medullary thyroid cancer (MTC). This study evaluated whether the preoperative serum calcitonin level in combination with ultrasonographic features of MTC can be used to assess the LN status as well as predict the risk of metastasis in patients with MTC.. We retrospectively analyzed the clinical data of 95 patients with MTC, and a nomogram model was constructed and validated. Using integrated database analysis of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), we mined pathways wherein. Correlation analysis revealed a significant association between the infiltrating range, diameter, calcification, blood flow, the preoperative serum calcitonin level, and metastasis. The metastasis risk-prediction model showed great accuracy in determining the risk of metastasis in MTC (area under the curve of the receiver operating characteristic [ROC] curve: 0.979 [95% confidence interval 0.946-1.000]). Decision curve analysis (DCA) showed that the model has excellent clinical utilization potential. Significantly,. The preoperative serum calcitonin level, in combination with ultrasonographic features, can be used to predict the risk of metastasis in patients with MTC and constitute a noninvasive accurate method for preoperative diagnosis of MTC.

Topics: Aged; Calcitonin Gene-Related Peptide; Carcinoma, Neuroendocrine; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Preoperative Period; Retrospective Studies; Risk Assessment; Thyroid Neoplasms; Ultrasonography

Topics: Amyloidosis; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma; Carcinoma, Neuroendocrine; Female; Humans; Kidney; Middle Aged; Thyroid Neoplasms

Serum procalcitonin (PCT) is a biomarker used routinely to diagnose infections. Some malignancies are usual false positives for PCT. However, its value and behavior in the setting of lung cancers are poorly known. The objective of this study was to assess PCT positivity in a lung cancer cases series.. Between November 2011 and September 2012, all cases of newly diagnosed lung cancer with a pre-antineoplastic PCT assay and no patent signs of infection were included in the study. All PCT levels were assessed by immunofluorescent assay in a single laboratory.. Eighty-nine patients were included (70.8% male; mean age 62; small-cell cancer 20.2%; stage IV cancer 60.7%). Overall, PCT was positive in 42%. A neuroendocrine component, having 2 or more metastatic sites, having a pleura or a liver metastasis, and being positive for CRP were all significantly associated with positive PCT in univariate analysis. In multivariate analysis, only the presence of a neuroendocrine component remained strongly associated with a positive PCT (AOR=7.24 [CI=95% 1.91-27.51]; P=0.004). Finally, baseline PCT levels <0.5 µg/l were found in 43% of NSCLC with a neuroendocrine component, vs. 9% of cancers with other histology (P=0.0001).. Lung cancer may cause false positives for procalcitonin, particularly in cases of neuroendocrine cancers or in the presence of multiple metastases. These results should be taken into account for PCT-based decisional algorithms.

Topics: Aged; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Neuroendocrine; False Positive Reactions; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Protein Precursors; Retrospective Studies; Time Factors

The clinical utility of procalcitonin has not been demonstrated across the whole spectrum of medullary thyroid cancer (MTC).. This serum biomarker validation study aimed at defining the diagnostic accuracy of procalcitonin for screening and risk stratification of MTC and delineating biochemical thresholds predictive of lymph node involvement in the neck and mediastinum.. This was a retrospective analysis at a tertiary referral center.. Included in this study were 457 consecutive patients with previously untreated MTC, 112 of whom had procalcitonin and calcitonin serum levels determined before the initial operation.. The intervention was compartment-oriented surgery.. Main outcome measures included primary tumor diameter, extrathyroidal extension, lymph node metastases, distant metastases, and biochemical cure.. Receiver operating characteristics analyses revealed similar diagnostic accuracy for procalcitonin vs the current calcitonin standard, yielding comparable areas under the curve for primary tumors at thresholds of 10 (0.94 vs 0.93) and 40 (0.92 vs 0.84) mm; extrathyroidal extension (0.84 vs 0.83), lymph node metastasis (0.88 vs 0.86), and distant metastasis (0.93 vs 0.91). Lymph node metastases were present in the ipsilateral lateral neck with procalcitonin levels ≤1.0 ng/mL and the ipsilateral central neck with procalcitonin levels ≤0.25 ng/mL. Above a threshold of 1.0 ng/mL, lymph node metastases emerged in the contralateral central and lateral neck and above 5.0 ng/mL also in the upper mediastinum. When procalcitonin levels exceeded 1, 5, 10, and 50 ng/mL, biochemical cure rates declined to no more than 71%, 36%, 23%, and 10%, respectively.. Serum procalcitonin, having comparable diagnostic accuracy, has great potential to replace serum calcitonin as a new standard of care in the management of MTC because it does not need to be kept cool on ice or frozen and is easier to manage at the community level.

Topics: Adult; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Neuroendocrine; Early Detection of Cancer; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Protein Precursors; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Thyroid Neoplasms

Serum calcitonin (sCT) is the main tumor marker for medullary thyroid cancer (MTC), but it has certain limitations. Various sCT assays may have important intra-assay or interassay variation and may yield different and sometimes conflicting results. A pentagastrin- or calcium-stimulation calcitonin (CT) test may be desirable in some situations. Alternatively, or in the absence of the stimulation test, mRNA detection offers the advantages of being more comfortable and less invasive; it only requires blood collection and has no side effects. The objective of this study was to investigate the applicability of measuring calcitonin-related polypeptide alpha (CALCA) gene transcripts (CT-CALCA and calcitonin gene-related peptide [CGRP]-CALCA) in patients with MTC and in relatives diagnosed with a RET mutation and to test mRNA as an alternative diagnostic tool for the calcitonin-stimulation test.. Twenty-three healthy controls and 26 individuals evaluated for MTC were selected, including patients with sporadic or hereditary MTC and RET mutation-carrying relatives. For molecular analysis, RNA was extracted from peripheral blood, followed by cDNA synthesis using 3.5 μg of total RNA. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed with SYBR Green and 200 nM of each primer for the two specific mRNA targets (CT-CALCA or CGRP-CALCA) and normalized with the ribosomal protein S8 as the reference gene.. We detected CALCA transcripts in the blood samples and observed a positive correlation between them (r=0.946, p<0.0001). Both mRNAs also correlated with sCT (CT-CALCA, r=0.713, p<0.0001; CGRP-CALCA, r=0.714, p<0.0001). The relative expression of CT-CALCA and CGRP-CALCA presented higher clinical sensitivity (86.67 and 100, respectively), specificity (97.06 and 97.06), positive predictive value (92.86 and 93.75), and negative predictive value (94.29 and 100), than did sCT (73.33, 82.35, 64.71, and 87.50, respectively). In addition, the CALCA transcript measurement mirrored the response to the pentagastrin test.. We demonstrate that the measurement of CALCA gene transcripts in the bloodstream is feasible and may refine the management of patients with MTC and RET mutation-carrying relatives. We propose considering the application of this diagnostic tool as an alternative to the calcitonin-stimulation test.

Topics: Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Neuroendocrine; Case-Control Studies; DNA, Complementary; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Mutation; Pentagastrin; Predictive Value of Tests; Protein Precursors; Proto-Oncogene Proteins c-ret; RNA, Messenger; Sensitivity and Specificity; Thyroid Neoplasms

To prospectively evaluate the role of procalcitonin (PCT) in detecting or excluding medullary thyroid carcinoma (MTC) among patients with thyroid nodules and increased calcitonin (CT) levels.. Fourteen of 1236 patients referred for thyroid nodules had increased serum CT >10 pg/mL. A stimulation test with pentagastrin was done and both CT and PCT were measured after stimulation. All patients underwent thyroid ultrasound, fine-needle cytology and, if indicated, surgery with histological and immunohistochemical examination of the surgical specimens.. After follow-up, two MTCs were found. These two patients had basal CT >100 pg/mL and detectable (>0.1 ng/mL) PCT, with 100% sensitivity. Pentagastrin stimulated CT achieved values above 100 pg/mL in two MTCs and in other two cases with no MTC outcome (50% PPV and 83% NPV). On the contrary, all patients with no MTC had both basal and stimulated undetectable PCT (100% PPV and 100% NPV).. The addition of basal PCT measurement in patients with thyroid nodule(s) and increased CT may significantly improve accuracy of CT measurement without needing a PG stimulation test.

Topics: Adult; Aged; Biomarkers, Tumor; Biopsy, Fine-Needle; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Neuroendocrine; Female; Humans; Male; Middle Aged; Pentagastrin; Predictive Value of Tests; Protein Precursors; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography