The use of various types of molecular markers for preoperative diagnostic of thyroid nodules
- Presentation Speakers / Moderators
Introduction. Analysis of molecular markers as an addition to cytological analysis of fine-needle aspiration is a promising approach for improving preoperative thyroid nodule diagnostics. The aim of our work was to develop an algorithm for preoperative detection and typing of thyroid nodules with a high throughput and acceptable accuracy based on a small set of molecular markers. Five types of molecular markers were involved: 5 somatic point mutations in BRAF, HRAS and NRAS genes and RET-PTC1 and PAX8-PPAR? translocations, expression level of the HMGA2 gene; expression level of 13 miRNAs; mitochondrial-to-nuclear DNA ratio.
Methods. Material of 494 cytological samples of thyroid gland was analyzed from 232 patients. The pathological reports for all samples were known, including: goiter – 105 samples, follicular adenoma – 101, follicular carcinoma – 43, Hürthle cell carcinoma – 25, papillary carcinoma – 121, follicular variant of papillary carcinoma – 80, medullary carcinoma – 19. The content of the above-listed markers was evaluated using Real-Time qPCR.
Results. The minimum set of markers is revealed providing a high-accuracy distinction (sensitivity=0.98; PPV=0.98) between benign and malignant neoplasms and reliably typing papillary (sensitivity=0,98; PPV=0,98), medullary (sensitivity=0.94; PPV=1.00), and Hürthle cell carcinomas (sensitivity=0.91; PPV=0.99) – expression level of the HMGA2 gene, miRNA-375, -221, -146b, the ratio of mitochondrial and nuclear DNA.
Conclusions. The study demonstrates the possibility of detecting and typing malignant thyroid tumors with high accuracy using a panel of a small number of molecular markers by a simple PCR-based method. Combining markers of different type made it possible to achieve higher quality of classification. This method can be applied in combination with cytological analysis, which can help reduce the number of additional punctures and unnecessary surgical interventions.
Two Approaches to Level 5 Neck Dissection
- Jeff Blumberg