scholarly journals Somatic mutation testing: the role in differential diagnosis of thyroid neoplasms

2019 ◽  
Vol 13 (1) ◽  
pp. 26-41
Author(s):  
Vera A. Kachko ◽  
Andrew R. Zaretsky ◽  
Vladimir E. Vanushko ◽  
Nadezhda M. Platonova ◽  
Aleksandr Yu. Abrosimov ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Blood Plasma ◽  
Treatment Strategy ◽  
Hot Spots ◽  
Thyroid Neoplasms ◽  
Mutation Testing ◽  
Thyroid Tumors ◽  
Braf Gene ◽  
Cytological Examination ◽  
Gene Exon

Background: In the preoperative diagnosis of thyroid tumors the cytological examination of the material of fine needle aspiration biopsy is the gold standard and serves as the basis for planning of treatment strategy. However, in 10–30% of cases, it cannot be clearly established by cytology whether the nature of thyroid neoplasm benign or malignant, which leads to the inability to choose the optimal treatment strategy in advance. For such cases, it is extremely important to search for methods of clarifying differential diagnosis, among which mutation testing is currently considered the most promising. Aims: To evaluate the possibility of using mutation tests for clarifying differential diagnosis of thyroid neoplasms at the preoperative stage. Materials and methods: We performed the prospective single center study, which included patients with the thyroid neoplasms, who had been treated in the Endocrinology Research Center, Moscow, Russia from 2012 to 2014. Samples of histological material, cytological material and blood plasma of these patients were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX. Results: The study included 75 patients, 29 of them with low-risk papillary thyroid cancer, 29 with follicular neoplasm NA of the thyroid gland and 17 with colloid nodular goiter. Mutations in the “hot spots” of the BRAF gene (exon 15, codon area 600–601) were found in 29 patients, mutations in the “hot spots” of the NRAS gene (exon 3, codon 61) – in 8 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. Correlation of the results of mutational testing of cytological and histological material was 91.7%. Mutations of tumor origin in circulating blood plasma DNA were found in only 1 cases. The prognostic value of the positive result (PPV) of the mutation test on cytological material in relation to the malignant nature of the thyroid tumor was 100% for the BRAF gene and 0% for the NRAS gene. Conclusions: The mutation test in the “hot spots” of the BRAF gene on cytological material can be used as an additional marker to clarify the nature of thyroid tumors, when the result of cytological examination are uncertain. Either in similar situations for mutation tests in the “hot spots” of genes KRAS, NRAS, EIF1AX and TERT on cytological material, or mutation testing of circulating DNA of blood plasma can’t be used as an additional marker.

scholarly journals The possibility of using freely circulating DNA blood plasma in preoperative diagnosis of thyroid tumors

2020 ◽  
Author(s):  
Vera Kachko ◽  
Vladimir Vanushko ◽  
Nadezhda Platonova ◽  
Aleksandr Abrosimov ◽  
Galina Snigireva ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Blood Plasma ◽  
Hot Spots ◽  
Somatic Mutations ◽  
Gene Mutations ◽  
Circulating Dna ◽  
Thyroid Tumors ◽  
Braf Gene ◽  
Gene Exon ◽  
In Blood Plasma

Background: The feasibility of using molecular genetic markers for the diagnosis of thyroid tumors and the impact on the prognosis of thyroid cancer are being actively investigated. The most interesting are genes, the detection of which is associated not only with thyroid cancer, but also with a more aggressive course of the disease. The ability to diagnose the molecular profile of minimally invasive methods with the study of freely circulating DNA tumor tissue in blood plasma is a modern trend of medicine. Aims: to evaluate the frequency of somatic mutations in the "hot spots" of BRAF, KRAS, KRAS, EIF1AX and TERT genes in circulating DNA of blood plasma. Materials and methods: Samples of DNA, extracted from the removed tumor and non-tumor thyroid tissue, were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX and then in identifying mutations and testing appropriate samples of free circulating DNA in blood plasma. Results: mutations in the" hot spots "of the BRAF gene (exon 15, codon area 600-601) were found in 54 patients, mutations in the" hot spots " of the NRAS gene (exon 3, codon 61) in 12 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. In freely circulating blood plasma DNA, BRAF gene mutations were detected in 1 case, NRAS gene mutations were detected in 1 case. Conclusions: the use of freely circulating DNA of blood plasma in the testing of the studied sample did not show the feasibility for the diagnosis of thyroid tumors.

scholarly journals A PCR-based expression signature of malignancy in follicular thyroid tumors

2007 ◽  
Vol 14 (2) ◽  
pp. 381-391 ◽  
Author(s):  
Theodoros Foukakis ◽  
Arief Gusnanto ◽  
Amy YM Au ◽  
Anders Höög ◽  
Weng-Onn Lui ◽  
...  
Keyword(s):  
High Risk ◽  
Gene Selection ◽  
Thyroid Neoplasms ◽  
Thyroid Tumors ◽  
Large Tumor ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Expression Levels ◽  
High Risk Disease ◽  
Follicular Thyroid Tumors

The diagnosis of follicular thyroid carcinoma (FTC) in the absence of metastasis can only be established postoperatively. Moreover, high-risk FTCs are often not identifiable at the time of diagnosis. In this study, we aimed to identify transcriptional markers of malignancy and high-risk disease in follicular thyroid tumors. The expression levels of 26 potential markers of malignancy were determined in a panel of 75 follicular thyroid tumors by a TaqMan quantitative RT-PCR approach. Logistic regression analysis (LRA) was used for gene selection and generation of diagnostic and prognostic algorithms. An algorithm based on the expression levels of five genes (TERT, TFF3, PPARγ, CITED1, and EGR2) could effectively predict high-risk disease with a specificity of 98.5%. The metastatic potential could be predicted in all four cases with apparently benign or minimally invasive (MI) disease at the time of diagnosis, but poor long-term outcome. In addition, a second model was produced by implementing two genes (TERT and TFF3), which was able to distinguish adenomas from de facto carcinomas. When this model was tested in an independent series of atypical adenomas (AFTA) and MI-FTCs, 16 out of 17 AFTAs were classified as ‘benign’, while MI-FTCs with vascular invasion (sometimes referred to as ‘moderately invasive’) and/or large tumor size tended to classify in the ‘malignant’ group. The reported models can be the foundation for the development of reliable preoperative diagnostic and prognostic tests that can guide the therapeutic approach of follicular thyroid neoplasms with indeterminate cytology.

Thyroid Peroxidase Immunohistochemistry in Differential Diagnosis of Thyroid Tumors

2006 ◽  
Vol 17 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Svetlana Savin ◽  
Dubravka Cvejic ◽  
Tijana Isic ◽  
Ivana Petrovic ◽  
Ivan Paunovic ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Thyroid Peroxidase ◽  
Thyroid Tumors

Ensuring the most effective strategy for cancer treatment of patients with brain tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14000-e14000
Author(s):  
Elena A. Sheiko ◽  
Elena M. Frantsiyants ◽  
Eduard E. Rostorguev ◽  
Irina V. Kaplieva ◽  
Valeria A. Bandovkina ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Brain Tumors ◽  
Blood Plasma ◽  
Histological Analysis ◽  
Malignant Tumors ◽  
Kinetic Method ◽  
Benign Tumors ◽  
Tumor Removal ◽  
Plastic Tube ◽  
Malignant Brain Tumors

e14000 Background: The purpose of the study was to analyze changes in the total activity of trypsin-like proteinases (TLPs) in the blood plasma in patients with brain tumors for the preoperative differential diagnosis of benign, primary and secondary malignant brain tumors. Methods: TLPs were measured in 164 patients with brain tumors. The blood had been collected from the patients in a standard plastic tube with 3.8% sodium citrate (9:1) 3 days prior to the surgery. Citrate blood was centrifuged; citrated plasma was obtained and used to determine the total TLP activity by the unified kinetic method. Results were compared with the data in donors. Results: TLP activity in 37 (22.6%) of 164 patients was within the normal range (258–402 IU/mL, on the average 333.0±27.1 IU/mL). Benign brain tumors (meningioma) were diagnosed in all 37 patients after the tumor removal and histological analysis. In 74 (45.1%) of 164 patients, TLP activity was within 1158–1626 IU/mL (on the average 1331.0±102.4 IU/mL, p < 0.05), i.e. 3.8-5.3 times higher than the norm in donors (malignancy coefficient on average 4.4±0.3 times). Primary malignant brain tumors (glioblastoma) were diagnosed in all 74 patients after the tumor removal and histological analysis. In 53 (32.3%) of 164 patients, TLP activity was within 1794–2868 IU/mL (on the average 2227.0±174.1 IU/mL, p < 0.05), i.e. 5.9-9.4 times higher than the norm in donors (malignancy coefficient on average 7.3±0.5 times). Secondary malignant brain tumors (metastases) were diagnosed in all 53 patients after the tumor removal and histological analysis. Conclusions: The specificity of the proposed method for the differential diagnosis of brain tumors was very high: for benign tumors - 97.2%, for primary malignant tumors - 98.6% and for secondary malignant tumors - 98.1%. So, TLP activity indices in the blood plasma are an informative auxiliary laboratory test that will help in clarifying and/or confirming the differential diagnosis of brain tumors.

scholarly journals Combined quantitation of HMGA2 mRNA, microRNAs, and mitochondrial-DNA content enables the identification and typing of thyroid tumors in fine-needle aspiration smears

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sergei E. Titov ◽  
Mikhail K. Ivanov ◽  
Pavel S. Demenkov ◽  
Gevork A. Katanyan ◽  
Eugenia S. Kozorezova ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Molecular Markers ◽  
Fine Needle Aspiration ◽  
Real Time Pcr ◽  
Thyroid Nodules ◽  
Nuclear Dna ◽  
Malignant Tumors ◽  
Needle Aspiration ◽  
Thyroid Tumors ◽  
Fine Needle

Abstract Background Analysis of molecular markers in addition to cytological analysis of fine-needle aspiration (FNA) samples is a promising way to improve the preoperative diagnosis of thyroid nodules. Nonetheless, in clinical practice, applications of existing diagnostic solutions based on the detection of somatic mutations or analysis of gene expression are limited by their high cost and difficulties with clinical interpretation. The aim of our work was to develop an algorithm for the differential diagnosis of thyroid nodules on the basis of a small set of molecular markers analyzed by real-time PCR. Methods A total of 494 preoperative FNA samples of thyroid goiters and tumors from 232 patients with known histological reports were analyzed: goiter, 105 samples (50 patients); follicular adenoma, 101 (48); follicular carcinoma, 43 (28); Hürthle cell carcinoma, 25 (11); papillary carcinoma, 121 (56); follicular variant of papillary carcinoma, 80 (32); and medullary carcinoma, 19 (12). Total nucleic acids extracted from dried FNA smears were analyzed for five somatic point mutations and two translocations typical of thyroid tumors as well as for relative concentrations of HMGA2 mRNA and 13 microRNAs and the ratio of mitochondrial to nuclear DNA by real-time PCR. A decision tree–based algorithm was built to discriminate benign and malignant tumors and to type the thyroid cancer. Leave-p-out cross-validation with five partitions was performed to estimate prediction quality. A comparison of two independent samples by quantitative traits was carried out via the Mann–Whitney U test. Results A minimum set of markers was selected (levels of HMGA2 mRNA and miR-375, − 221, and -146b in combination with the mitochondrial-to-nuclear DNA ratio) and yielded highly accurate discrimination (sensitivity = 0.97; positive predictive value = 0.98) between goiters with benign tumors and malignant tumors and accurate typing of papillary, medullary, and Hürthle cell carcinomas. The results support an alternative classification of follicular tumors, which differs from the histological one. Conclusions The study shows the feasibility of the preoperative differential diagnosis of thyroid nodules using a panel of several molecular markers by a simple PCR-based method. Combining markers of different types increases the accuracy of classification.

Criteria of Clinical and Radiological Diagnosis in Nonpuerperal Acute Phlogistic-Like Processes of the Breast: Considerations on 97 Consecutive Cases

1981 ◽  
Vol 67 (1) ◽  
pp. 31-34
Author(s):  
Gaetano Cardona ◽  
Stefano Ciatto
Keyword(s):  
Differential Diagnosis ◽  
Diagnostic Criteria ◽  
False Positive ◽  
Nipple Discharge ◽  
Needle Aspiration ◽  
Radiological Examination ◽  
Radiological Diagnosis ◽  
Cytological Examination ◽  
Outer Quadrant ◽  
Radiological Evidence

The authors report a series of 97 cases of phlogistic-like process of the breast. Clinical and radiological signs and criteria of differential diagnosis between benign phlogosis and cancer are investigated. The location in the areolar/periareolar region, the presence of fever, and the radiological evidence of limited skin thickening were the features more significantly correlated with benign phlogosis, while cancer should be suspected in the case of lesions located in the upper-outer quadrant and in presence of a diffuse skin thickening at radiological examination. These diagnostic criteria seem particularly useful since the typical clinical or radiological signs of cancer are present only in 50 % of cancer cases. The cytological examination of nipple discharge or needle aspiration fluid is of particular help: no false positive or negative cases were observed in a series of 42 examined patients.

scholarly journals Pitfalls in Challenging Thyroid Tumors: Emphasis on Differential Diagnosis and Ancillary Biomarkers

2020 ◽  
Vol 31 (3) ◽  
pp. 197-217
Author(s):  
José Manuel Cameselle-Teijeiro ◽  
Catarina Eloy ◽  
Manuel Sobrinho-Simões
Keyword(s):  
Differential Diagnosis ◽  
Thyroid Tumors

Cytology of follicular thyroid tumors, quality assurance, and differential diagnosis

2010 ◽  
Vol 49 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Miyoko MAEKAWA ◽  
Mitsuyoshi HIROKAWA ◽  
Yukari YANASE ◽  
Seiji KUMA ◽  
Akira MIYAUCHI
Keyword(s):  
Quality Assurance ◽  
Differential Diagnosis ◽  
Thyroid Tumors ◽  
Follicular Thyroid Tumors
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