TY - JOUR

T1 - Validation of preoperative diagnosis of malignant thyroid tumors using a molecular classifier

AU - Titov, Sergey Evgenievich

AU - Lukyanov, Sergey Anatolyevich

AU - Kozorezova, Evgeniya Sergeevna

AU - Demenkov, Pavel Sergeevich

AU - Sergiyko, Sergey Vladimirovich

AU - Veryaskina, Yulia Andreevna

AU - Vorobyov, Sergey Leonidovich

AU - Sleptsov, Ilya Valeryevich

AU - Gostimsky, Alexander Vadimovich

N1 - Публикация для корректировки.

PY - 2022

Y1 - 2022

N2 - Background. Fine needle aspiration biopsy (FNA) of thyroid nodules under ultrasound control followed by cytological examination is the main method to assess the risk of malignancy of these formations. At the same time, vague and suspicious cytological findings (Bethesda III, IV) are indications for referring patients for surgical treatment, and in some cases this will be excessive. The analysis of molecular markers in the FNA material in addition to cytological examination is a promising way to improve the preoperative diagnosis of thyroid nodules. Aim. The aim of the study was improving accuracy of preoperative diagnosis of thyroid tumors. Materials and methods. The validation of the diagnostic capabilities of the domestic molecular genetic test (MGT), developed for the differential diagnosis of thyroid tumors, was carried out on the basis of a retrospective multicenter blind study. The test was based on the assessment of the relative levels of expression of GCM2 and HMGA2 genes, microRNA levels -146b, -221, -375, -31 and -551b, the ratio of mitochondrial and nuclear DNA, as well as the determination of somatic mutation V600E in the BRAF gene. 329 cytological samples were analyzed, which included: 22 (6.7%) with the conclusion of Bethesda II, 226 (68.7%) of Bethesda IV, 6 (1.8%) of Bethesda V, and 75 (22.8%) of Bethesda VI. Results. The following diagnostic characteristics were obtained for detection of malignant tumors by means of a molecular test in the study: specificity ― 90.8%, sensitivity ― 86.9%, positive predictive value ― 82.3%, negative predictive value ― 93.4%. The overall accuracy was 96.6% for detecting of papillary cancer with the molecular test, 94.4% for follicular cancer, 100% for medullary cancer, and 96.9% for Hürthle cell carcinoma. Conclusion. The performed study demonstrates the possibility of detecting and typing thyroid tumors with the use of a panel of a small number of molecular markers detected in cytological preparations with real-time PCR. The accuracy of the domestic MGТ is comparable with foreign analogues.

AB - Background. Fine needle aspiration biopsy (FNA) of thyroid nodules under ultrasound control followed by cytological examination is the main method to assess the risk of malignancy of these formations. At the same time, vague and suspicious cytological findings (Bethesda III, IV) are indications for referring patients for surgical treatment, and in some cases this will be excessive. The analysis of molecular markers in the FNA material in addition to cytological examination is a promising way to improve the preoperative diagnosis of thyroid nodules. Aim. The aim of the study was improving accuracy of preoperative diagnosis of thyroid tumors. Materials and methods. The validation of the diagnostic capabilities of the domestic molecular genetic test (MGT), developed for the differential diagnosis of thyroid tumors, was carried out on the basis of a retrospective multicenter blind study. The test was based on the assessment of the relative levels of expression of GCM2 and HMGA2 genes, microRNA levels -146b, -221, -375, -31 and -551b, the ratio of mitochondrial and nuclear DNA, as well as the determination of somatic mutation V600E in the BRAF gene. 329 cytological samples were analyzed, which included: 22 (6.7%) with the conclusion of Bethesda II, 226 (68.7%) of Bethesda IV, 6 (1.8%) of Bethesda V, and 75 (22.8%) of Bethesda VI. Results. The following diagnostic characteristics were obtained for detection of malignant tumors by means of a molecular test in the study: specificity ― 90.8%, sensitivity ― 86.9%, positive predictive value ― 82.3%, negative predictive value ― 93.4%. The overall accuracy was 96.6% for detecting of papillary cancer with the molecular test, 94.4% for follicular cancer, 100% for medullary cancer, and 96.9% for Hürthle cell carcinoma. Conclusion. The performed study demonstrates the possibility of detecting and typing thyroid tumors with the use of a panel of a small number of molecular markers detected in cytological preparations with real-time PCR. The accuracy of the domestic MGТ is comparable with foreign analogues.

KW - follicular thyroid tumor

KW - molecular genetic testing

KW - thyroid cancer

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85163189738&origin=inward&txGid=5e150e98a261a28f2fe7c048ef6879d7

UR - https://www.mendeley.com/catalogue/7c45c6fd-42fd-368f-9c0c-444319edd54c/

U2 - 10.37469/0507-3758-2022-68-6-741-751

DO - 10.37469/0507-3758-2022-68-6-741-751

M3 - Article

VL - 68

SP - 741

EP - 751

JO - Voprosy Onkologii

JF - Voprosy Onkologii

SN - 0507-3758

IS - 6

ER -