scholarly journals MicroRNAs – promising molecular markers for detecting cancer in thyroid nodules

2018 ◽  
Vol 14 (3) ◽  
pp. 140-148
Author(s):  
Olga S. Serdyukova ◽  
Sergei E. Titov ◽  
Ekaterina S. Malakhina ◽  
Oksana D. Rymar

Thyroid nodules are one of the most common thyroid diseases. The prevalence of thyroid nodules is estimated to be 2–65% depending on the detection methods. Yet despite the high frequency of thyroid nodules only about 5–10% of such nodules are malignant. Fine needle aspiration cytology of the thyroid nodule is currently the primary diagnostic tool for determining the nature of a thyroid nodule. Now, the fine needle aspiration biopsy is the gold standard for diagnosing thyroid cancer but in 30% of cases the cytological conclusion is uncertain. Cytological research is not enough to diagnose benign and malignant tumors. The need to improve the effectiveness of fine needle aspiration biopsy findings led to the search for new diagnostic biomarkers and the creation of diagnostic panels on their basis for their application in the diagnosis of uncertain nodules. Determination of molecular markers in the thyroid aspirate will allow to differentiate benign and malignant tumors more accurately at the preoperative stage and reduce the number of inappropriate surgery. The review article presents the characteristics of MicroRNAs, allowing them to be used in preoperative diagnosis of thyroid nodules. Diagnostic panels based on gene mutations and MicroRNA expression demonstrating high sensitivity and specificity of these methods are also indicated. Analysis of literature indicates that molecular analysis of fine needle aspiration genetic material from thyroid nodal formations demonstrates great prospects of prognosis, diagnosis and treatment of thyroid cancer. However, there is no sufficient evidence to recommend or to prohibit of utilization this molecular testing during the cytological conclusion of indeterminate thyroid nodules. Molecular analysis (MicroRNA) is a perspective method for evaluation of thyroid nodal formations with indeterminate cytology, however, this method requires further study and improvement.

2020 ◽  
Vol 26 (11) ◽  
pp. 1286-1290
Author(s):  
Edy Kornelius ◽  
Shih-Chang Lo ◽  
Chien-Ning Huang ◽  
Yi-Sun Yang

Objective: There are conflicting data on the risk of thyroid cancer in thyroid nodules 3 cm or larger, and few such studies on this issue have been conducted in Asia. This study aimed to examine the risk of thyroid cancer in patients with thyroid nodules 3 cm or larger. Methods: This was a 7-year retrospective study conducted in a tertiary referral hospital in Taiwan. All patients with a thyroid nodule measuring ≥3 cm who underwent thyroid operation with or without fine-needle aspiration biopsy (FNAB) were included. The prevalence rate of thyroid cancer, as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false-negative rate of FNAB for thyroid nodule ≥3 cm were also examined. Results: A total of 132 patients were included in this study. Thyroid cancer was detected in 19 of 132 (14.4%) thyroid nodules measuring ≥3 cm. The performance of FNAB for detecting cancer in nodules 3 cm or larger without considering other ultrasonography parameters was relatively poor with a sensitivity of 50%, but the specificity (100%), PPV (100 %), and NPV (93.4 %) were excellent. Conclusion: The risk of thyroid cancer for thyroid nodules ≥3 cm in this study was low. The PPV and NPV of FNAB were high for the detection of cancer in large nodules. The decision to perform thyroidectomy should not be solely based on nodule size and should include other factors, such as ultrasound characteristics and surgical risk. Abbreviations: ATA = American Thyroid Association; FNAB = fine-needle aspiration biopsy; mPTC = micropapillary thyroid carcinoma; NPV = negative predictive value; PPV = positive predictive value; PTC = papillary thyroid carcinoma


2011 ◽  
Vol 135 (5) ◽  
pp. 569-577 ◽  
Author(s):  
Yuri E. Nikiforov

Abstract Context.—Thyroid cancer is the most common type of endocrine malignancy and its incidence is steadily increasing. Papillary carcinoma and follicular carcinoma are the most common types of thyroid cancer and represent those tumor types for which use of molecular markers for diagnosis and prognostication is of high clinical significance. Objective.—To review the most common molecular alterations in thyroid cancer and their diagnostic and prognostic utility. Data Sources.—PubMed (US National Library of Medicine)–available review articles, peer-reviewed original articles, and experience of the author. Conclusions.—The most common molecular alterations in thyroid cancer include BRAF and RAS point mutations and RET/PTC and PAX8/PPARγ rearrangements. These nonoverlapping genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. These molecular alterations can be detected in surgically resected samples and fine-needle aspiration samples from thyroid nodules and can be of significant diagnostic use. The diagnostic role of BRAF mutations has been studied most extensively, and recent studies also demonstrated a significant diagnostic utility of RAS, RET/PTC, and PAX8/PPARγ mutations, particularly in thyroid fine-needle aspiration samples with indeterminate cytology. In addition to the diagnostic use, BRAF V600E mutation can also be used for tumor prognostication, as this mutation is associated with higher rate of tumor recurrence and tumor-related mortality. The use of these and other emerging molecular markers is expected to improve significantly the accuracy of cancer diagnosis in thyroid nodules and allow more individualized surgical and postsurgical management of patients with thyroid cancer.


2020 ◽  
Vol 26 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Ngan Betty Lai ◽  
Dave Garg ◽  
Anthony P. Heaney ◽  
Marvin Bergsneider ◽  
Angela M. Leung

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.). Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology. Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 [SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 [SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed). Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly. Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sergei E. Titov ◽  
Mikhail K. Ivanov ◽  
Pavel S. Demenkov ◽  
Gevork A. Katanyan ◽  
Eugenia S. Kozorezova ◽  
...  

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.


2008 ◽  
Vol 93 (11) ◽  
pp. 4175-4182 ◽  
Author(s):  
Erik K. Alexander

Background: Fine-needle aspiration remains the primary diagnostic intervention for the evaluation of most thyroid nodules larger than 1–1.5 cm. Although most aspirates provide diagnostic cytology, approximately 15–25% will be classified indeterminate (often referred to as follicular neoplasm, suspicious for carcinoma, or atypical). In such cases, abnormal cellular findings preclude interpretation of benignity, although only a minority will prove cancerous upon final histopathology. Nonetheless, patients with indeterminate aspirates are commonly referred for consideration of hemi- or near-total thyroidectomy. Recently, improved understanding and novel investigation of clinical, radiological, cytological, and molecular factors has allowed improved stratification of cancer risk. Conclusion: Although surgery continues to be commonly recommended, strategies for such patients should increasingly seek to define treatment based on the estimation of an individual’s thyroid cancer risk in comparison with associated operative risk and morbidity. In doing so, the rate of unnecessary surgical procedures and associated complications can be reduced.


Author(s):  
Ali Murat Koç ◽  
Zehra Hilal Adıbelli ◽  
Zehra Erkul ◽  
Yasemin Şahin

Objective: Thyroid nodule is the most common disease of the thyroid gland and is closely associated with thyroid cancer. The gold standard method in diagnosis is Fine Needle Aspiration Biopsy (FNAB). Although the relationship between nodules containing microcalcification and malignancy is well known, there is no consensus on the relation of nodules with macrocalcification to malignancy and the adequacy of FNAB. In this study, it was aimed to compare the results of FNAB of nodules with and without macrocalcification in US examination. Methods: In this retrospective study, 466 nodules undergoing FNAB of 450 patients who applied for biopsy were included in the study. The demographic characteristics of the patients, US features of the nodules and cytopathology results of FNAB in the Bethesda classification were recorded. Nodules were divided into two main groups as calcified and non-calcified. US features and cytopathology results of the groups were compared. Results: Transverse sizes of calcified nodules were found to be larger than non-calcified ones (p = 0.003). In addition, solid composition, hypoechoic and prominent hypoechoic echogenicity, and irregular border feature were found with a higher rate in the calcified group (p <0.001). No significant difference was found between insufficient sample/non-diagnostic cytology (Bethesda-1) ratios in both groups (19.2% and 14.7%). Cytopathologically, number of malignant and suspected malignant nodules (Bethesda 5 and 6) were found to be higher in the calcified group (p=0.05). Conclusion: According to the results of this study, detection of macrocalcification in thyroid nodules in US examination does not cause a significant increase in insufficient FNAB results. However, the presence of macrocalcification increases the risk of malignancy of the thyroid nodule.


2007 ◽  
Vol 5 (4) ◽  
pp. 0-0
Author(s):  
Edita Mišeikytė Kaubrienė ◽  
Albertas Ulys ◽  
Mantas Trakymas ◽  
Jolita Rimienė

Edita Mišeikytė Kaubrienė1,  Albertas Ulys1, Mantas Trakymas1,  Jolita Rimienė21 Vilniaus universiteto Onkologijos institutas, Santariškių g. 1, LT-08660 Vilnius2 Valstybinis patologijos centras, Santariškių g. 1, LT-08660 VilniusEl paštas: [email protected] Plonos adatos aspiracinė biopsija yra patikimiausias skydliaukės mazgų diagnostikos metodas („aukso standartas“). Plonos adatos aspiracinė biopsinė – tai pradinis čiuopiamų ir nečiuopiamų skydliaukės mazgų stebėjimo ir gydymo strategijos žingsnis. Šio diagnostikos metodo patikimumui turi įtakos tyrėjų, atliekančių aspiracines biopsijas ir citologinius tyrimus, įgūdžiai, ypač svarbūs diferencijuojant nepiktybinius ir piktybinius folikulinius pakitimus. Tyrimas leidžia sumažinti dėl mazginės strumos atliekamų tiroidektomijų skaičių. Šios literatūros apžvalgos tikslas – įvertinti plonos adatos aspiracinės biopsijos reikšmę diagnozuojant skydliaukės mazgus. Straipsnyje pateikiamas plonos adatos aspiracinės biopsijos rezultatų įvertinimas. Daroma išvada, kad skydliaukės mazgų plonos adatos aspiracinė biopsija yra saugus, nebrangus, minimaliai invazinis ir informatyvus tyrimo metodas. Pagrindiniai žodžiai: skydliaukės mazgas, skydliaukės vėžys, ultragarsinis tyrimas, plonos adatos aspiracinė biopsijaFine-needle aspiration biopsy in thyroid cancer diagnostics Edita Mišeikytė Kaubrienė1,  Albertas Ulys1, Mantas Trakymas1,  Jolita Rimienė21 Institute of Oncology Vilnius University, Santariškių str. 1, LT-08660 Vilnius, Lithuania2 National Center of Pathology, Santariškių str. 1, LT-08660 Vilnius, LithuaniaE-mail: [email protected] Fine-needle aspiration biopsy is considered the most reliable test, a “gold standard” for the diagnosis of thyroid nodules. Fine-needle aspiration biopsy has made its mark as an initial diagnostic step in the management of palpable and nonpalpable thyroid nodules. Limitations of fine-needle aspiration are related to the skill of the aspirator, the expertise of the cytologist, and the difficulty in distinguishing some benign cellular adenomas from their malignant counterparts. This technique has resulted in an overall decline in the number of thyroidectomies performed for thyroid nodules. The objective of the article is to review the literature on the utility of fine-needle aspiration biopsy in the diagnostic management of nodular thyroid disease. Fine-needle aspiration biopsy of the thyroid gland is a safe, inexpensive, minimally invasive and highly accurate test in the diagnosis of nodular thyroid disease. Keywords: thyroid nodule, thyroid cancer, ultrasound, fine-needle aspiration biopsy


2006 ◽  
Vol 29 (10) ◽  
pp. 947-948 ◽  
Author(s):  
U. M. Musharrafieh ◽  
M. P. Nasrallah ◽  
R. A. Sawaya ◽  
Z. M. Hijazi ◽  
M. C. Haddad

2019 ◽  
Vol 103 (1-2) ◽  
pp. 9-14
Author(s):  
Bahadır Öz ◽  
Serap Doğan ◽  
Ertan Emek ◽  
Muhammed Akyüz ◽  
Alper Akcan ◽  
...  

The objective of the current study was to determine the risk of malignancy in patients with thyroid nodules with cytology of indeterminate follicular and indeterminate Hürthle cell neoplasm (HN). The cytologic diagnosis of follicular neoplasm (FN) or HN remains a diagnostic challenge. Often, surgery is recommended for such lesions. A retrospective analysis was performed on 80 patients who underwent thyroid surgery following a diagnosis of indeterminate FN and indeterminate HN in thyroid fine-needle aspiration biopsy. Sex; age; family history of thyroid cancer and radiation exposure; coexisting thyroid conditions, such as solitary nodule; multinodularity; cytologic diagnosis; sonographic features; type of surgical treatment; and histopathologic results were recorded. Of the 80 patients, 52 (65%) had FN on fine-needle aspiration biopsy cytology and 28 (35%) had HN. A total of 23 patients (28.7%) had primary thyroid cancers on surgical pathology, and 57 (71.3%) had benign diagnoses. Univariate analysis showed no differences between the benign and malignant groups by sex, nodule size, family history of thyroid cancer, history of radiation exposure, presence of solitary nodule or multinodularity in the nodular features. In multivariate binary logistic regression analysis, the factors that were statistically significant predictors of malignancy were microcalcification [odds ratio (OR), 10.9; 95% confidence interval (CI), 2.18–54.7; P = 0.004], being older than 45 years (OR, 4.2; 95% CI, 1.25–14.63; P = 0.02]. The independent predictors of malignancy in FN and HN are micorcalcification and being older than 45 years, the use of which may predict the risk of thyroid cancer.


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