cyclin-d1 and Thyroid-Nodule

Topics: Adult; Aged; Biopsy, Fine-Needle; Cyclin D1; Female; Humans; Male; Middle Aged; Molecular Diagnostic Techniques; Thyroid Nodule

Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodules; however, some features such as atypia of undetermined significance or follicular lesion of undetermined significance can confound efforts to identify malignancies. Similar to BRAF, cyclin D1 may be a strong marker of cell proliferation.. One hundred two patients with thyroidal nodule were enrolled in this prospective study. Expression of cyclin D1 in thyroid nodules was determined by immunohistochemistry using both surgical specimens and their cytological specimens. The identification of the optimal cut off points for the diagnosis of malignancy were evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) of markers were evaluated from crosstabs based on cut off points and significance were calculated. We also analyzed genetic variants by target NGS for thyroid nodule samples.. The positive predictive value (PPV) and median stain ratio (MSR) of cyclin D1 nuclear staining was determined in papillary thyroid carcinoma (PPV = 91.5%, MSR = 48.5%), follicular adenoma (PPV = 66.7%, MSR = 13.1%), and adenomatous goiter and inflammation controls (MSR = 3.4%). In FNA samples, a threshold of 46% of immunolabelled cells allows to discriminate malignant lesions from benign ones (P < 0.0001), with 81% sensitivity and 100% specificity. A 46% cutoff value for positive cyclin D1 immunostaining in thyroid cells demonstrated 81% sensitivity and 100% specificity. In surgical specimens, ROC curve analysis showed a 5.8% cyclin D1 immunostaining score predicted thyroid neoplasms at 94.4% sensitivity and 92.3% specificity (P = 0.003), while a 15.7% score predicted malignancy at 86.4% sensitivity and 80.5% specificity (P < 0.0001). Finally, three tested clinico-pathological variables (extra thyroidal extension, intraglandular metastasis, and lymph node metastasis) were significant predictors of cyclin D1 immunostaining (P < 0.001).. Our cytological cyclin D1 screening system provides a simple, accurate, and convenient diagnostic method in precision medicine enabling ready determination of personalized treatment strategies for patients by next generation sequencing using cytological sample.

Topics: Adenocarcinoma, Follicular; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Fine-Needle; Cell Nucleus; Child; Cyclin D1; DNA Mutational Analysis; Female; Goiter, Nodular; Humans; Immunohistochemistry; Male; Middle Aged; Precision Medicine; Predictive Value of Tests; Prospective Studies; ROC Curve; Thyroid Cancer, Papillary; Thyroid Gland; Thyroid Nodule; Tissue Array Analysis; Young Adult

To identify the role of gene products associated with apoptosis and cell cycle in the pathogenesis of thyroid follicular neoplasm.. Thirty follicular adenomas (FAs), 16 follicular carcinomas (FCs), and 20 adenomatous nodules (ANs) were investigated with immunohistochemical staining of p16, p21, p27, p53, Bcl-2, Bax, Bcl-xL, and cyclin D1 via a tissue microarray method.. Bcl-2 showed a significant difference between the benign groups (AN and FA) and the malignant group (FC). Bax was significantly higher in the FC group. p53 was lowest in the AN group and highest in the FC group with significant differences between the groups. p16 was significantly higher in the FC group than in the other groups. There was a significant difference between the AN group and neoplastic lesions in terms of p21 staining. The number of cases with positive p27 was lower in the AN group than the neoplastic groups. There was no significant difference in terms of Bcl-xL and cyclin D1.. Cell cycle modulators, led by the Bcl-2 family, played an important role in the pathogenesis of thyroid follicular neoplasm, and p53, p16, and p21 in particular played a role in the carcinogenesis of FC.

Topics: Adenocarcinoma, Follicular; Adenoma; Adult; Apoptosis; bcl-2-Associated X Protein; Cell Cycle Checkpoints; Cell Cycle Proteins; Cyclin D1; Female; Humans; Hyperplasia; Immunohistochemistry; Male; Middle Aged; Thyroid Neoplasms; Thyroid Nodule; Tissue Array Analysis

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC). The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.

Topics: Adenocarcinoma, Follicular; Biomarkers, Tumor; Carcinoma, Papillary, Follicular; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p27; Diagnosis, Differential; Galectin 3; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Keratin-19; Keratins; Sensitivity and Specificity; Thyroid Gland; Thyroid Nodule