Abstract
BackgroundFine-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.MethodsOne 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.ResultsThe 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).ConclusionOur 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.
Highlights
Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodules; some features such as atypia of undetermined significance or follicular lesion of undetermined significance can confound efforts to identify malignancies
There are no established criteria for the presurgical diagnosis of noninvasive follicular thyroid neoplasms such as a well-differentiated thyroid tumor of uncertain malignant potential, and its distinction from a follicular adenoma and/or classic papillary thyroid carcinoma [5, 6]
We found no evidence of CCND1 copy number change in any cases, which included 35 thyroidal tumors (PTC:21, follicular carcinomas (FC): 5, follicular adenomas (FA): 3, anaplastic thyroid carcinomas (ATC): 4, and with uncertain malignant potential (WP): 2)
Summary
Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodules; some features such as atypia of undetermined significance or follicular lesion of undetermined significance can confound efforts to identify malignancies. Thyroid nodules are defined as nodules originally detected in a patient with no thyroid-related clinical symptoms, examination findings, or suspected thyroid disease. These nodules are most commonly detected from medical imaging procedures, such as computed tomography, magnetic resonance imaging, and positron emission tomography, of the neck [1, 2]. Fine-needle aspiration (FNA) is the most reliable method to detect thyroid nodules; ultrasound detects solid hypoechoic features that are more likely to be malignant, with a sensitivity and specificity of 80 and 70%, respectively [3]. There are no established criteria for the presurgical diagnosis of noninvasive follicular thyroid neoplasms such as a well-differentiated thyroid tumor of uncertain malignant potential, and its distinction from a follicular adenoma and/or classic papillary thyroid carcinoma [5, 6]
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