Thyroid Follicular Adenoma Research Articles

Follicular adenoma of the thyroid gland in children: a clinical spectrum

IntroductionSurgical diseases of the thyroid gland in children are rare in comparison with those in the adult population. The aim of the study was to assess clinical aspects of thyroid follicular adenoma in children and attempt to develop a management algorithm that is useful in clinical practice.Material and methodsThe clinical database of all children operated on due to thyroid disease in the years 1993–2018 at the university pediatric surgical center was reviewed. The children in whom the postoperative histology report showed follicular adenoma were selected and their medical files were analyzed in detail. Clinical course of the disease, medical and family history, results of imaging studies, details of surgical management and final outcome were assessed in each case.ResultsAmong 183 children operated on for thyroid pathology in the study period there were 56 patients with follicular adenoma (30.6%). Their age ranged from 7 to 18 years. Seven patients were found to be hypothyroid and a further seven showed hyperthyroid status initially. Ultrasound scan showed a solitary nodule in 37 children (66.1%). Multiple nodules in one lobe were detected in 5 patients, while a further 14 children showed bilateral thyroid pathology. The result of preoperative cytologic examination was suspicious in 12 children (21.4%). All children were subjected to operative management. Forty-two children (75%) underwent at least unilateral total lobectomy. No patient showed a recurrent thyroid disease.ConclusionsFollicular adenoma in children presents a wide clinical and morphological spectrum. High incidence of associated diseases of other systems and congenital anomalies of the thyroid gland may indicate a complex etiology of follicular adenoma with participation of still unknown endogenic factors in children.

A network-based approach to identify key genes between follicular thyroid cancer and follicular thyroid adenoma

It is difficult to differentiate follicular thyroid cancer (FTC) from follicular thyroid adenoma (FTA) using fine-needle aspiration and imaging. This study aims to identify potential biomarkers to distinguish FTC from FTA. In recent years, microarray technology had a significant impact on our understanding of gene expression patterns in various diseases. Through analyzing microarray data along with bioinformatics, potential biomarkers can be identified in a query disease. To analyze the differentially expressed genes (DEGs), a gene expression profile of follicular thyroid tumors (GSE82208) was downloaded from gene expression omnibus (GEO). GO term and KEGG pathway enrichment analysis were carried out using Enrichr. To visualize the interaction of DEGs, we constructed a protein-protein interaction (PPI) network. Betweenness centrality was considered as the main criteria to identify hub genes. Based on GO term results DEGs are related to the cellular response to cadmium ion, metal ion binding, and focal adhesion. Moreover, KEGG pathway enrichment analysis demonstrated that DEGs are associated with Mineral absorption, Fluid shear stress, and atherosclerosis. Finally, CDH1, CDC42, JUN, FOS, KLF4, CTGF, and PAX8 genes were considered as potential biomarkers to differentiate FTC from FTA.

Sonographic Features Differentiating Follicular Thyroid Cancer from Follicular Adenoma–A Meta-Analysis

Simple SummaryThe risk of thyroid malignancy assessment may include certain ultrasound features. The analysis is lacking for the differentiation of follicular thyroid adenomas and cancers (FTAs and FTCs). Our meta-analysis aimed to identify sonographic features suggesting malignancy in the case of follicular lesions, potentially differentiating FTA and FTC. Based on twenty studies describing sonographic features of 10,215 nodules, we found that the most crucial feature associated with an increased risk of FTC were tumor protrusion (odds ratios—OR = 10.19), microcalcifications or mixed type of calcifications: 6.09, irregular margins: 5.11, marked hypoechogenicity: 4.59, and irregular shape: 3.6.Certain ultrasound features are associated with an increased risk of thyroid malignancy. However, they were studied mainly in papillary thyroid cancers (PTCs); these results cannot be simply extrapolated for the differentiation of follicular thyroid adenomas and cancers (FTAs and FTCs). The aim of our study was to perform a meta-analysis to identify sonographic features suggesting malignancy in the case of follicular lesions, potentially differentiating FTA and FTC. We searched thirteen databases from January 2006 to December 2020 to find all relevant, full-text journal articles written in English. Analyses assessed the accuracy of malignancy detection in case of follicular lesions, potentially differentiating FTA and FTC included the odds ratio (OR), sensitivity, specificity, positive and negative predictive values. A random-effects model was used to summarize collected data. Twenty studies describing sonographic features of 10,215 nodules met the inclusion criteria. The highest overall ORs to increase the risk of malignancy were calculated for tumor protrusion (OR = 10.19; 95% confidence interval: 2.62–39.71), microcalcifications or mixed type of calcifications (coexisting micro and macrocalcifications): 6.09 (3.22–11.50), irregular margins: 5.11 (2.90–8.99), marked hypoechogenicity: 4.59 (3.23–6.54), and irregular shape: 3.6 (1.19–10.92). The most crucial feature associated with an increased risk of FTC is capsule protrusion, followed by the presence of calcifications, irrespectively of their type.

CK19 and HBME-1 Expression as Diagnostic Test in Benign and Malignant Thyroid Lesions

BackgroundThyroid carcinoma is the most common malignancy of the endocrine system. Some cases histopathologically have overlappingmorphological features among papillary thyroid carcinoma follicular variants and follicular adenomas; beetween nodular hyperplasiaand protruding papillary protrusion; nuclear feature and thyroid papillary carcinoma. The combination of CK19 and HBME-1imunohistochemical staining have been proven as specific and sensitive markers to distinguish benign and malignant lesions thyroid.The purpose of this study was to determine the differences in CK19 and HBME-1 expression in benign and malignant Thyroid lesions.MethodsThis study used a diagnostic test of 50 cases (16 cases of nodular hyperplasia, 8 cases of follicular adenoma, 21 papillary thyroidcarcinomas and 5 cases of thyroid follicular carcinoma) clinicopathological data were noted. Immunohistochemical staining wasperformed using CK19 and HBME-1antibodies and the their expression assessed. Data were analysed by SPSS version 22.0.ResultsBased on the four histopathological diagnoses, the majority patient, were females between 20-50 years.Fifty percent of macroscopicsample size was more than 5 cm. The expression of CK19 and HBME-1 has a sensitivity value of 76.9% and 92.3% and a specificityvalue of 79.2% and 79.2%, consecutively. While positive predictive value 80% and 82.8% and negative predictive value 76% and90.5%, accuracy of 78% and 86%, respectively.ConclusionHBME-1 expression could be used to distinguishing benign from malignan lesions of thyroid with high diagnostic sensitivity thanCK19 expression.

Development and Validation of a Diagnostic Nomogram for the Preoperative Differentiation Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenomas.

The aim of the study was to construct and validate a nomogram for differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). Two hundred patients with pathologically confirmed thyroid follicular neoplasms were retrospectively analyzed. The patients were randomly divided into a training set (n = 140) and validation set (n = 60). Baseline data including demographics, CT (computed tomography) signs, and radiomic features were analyzed. Predictive models were developed and compared to build a nomogram. The predictive effectiveness of it was evaluated by the area under receiver operating characteristic curve (AUC). The CT model, radiomic model and combination model showed excellent discrimination (AUCs [95% confidence interval] = 0.847 [0.766-0.928], 0.863 [0.746-0.932], 0.913 [0.850-0.975]). The nomogram based on the combination model showed remarkable discrimination in the training and validation sets. The calibration curves suggested good consistency between actual observation and prediction. This study proposed a nomogram that can accurately and intuitively predict the malignancy potential of follicular thyroid neoplasms.

Thyroid Follicular Adenoma with Tracheal Stenosis

Some cases of thyroid malignant tumors and thyroid lymphoma were reported to have caused tracheal stenosis and choking. Benign thyroid tumors with dyspnea due to tracheal stenosis are very rare. We experienced a benign thyroid tumor that caused tracheal stenosis and dyspnea. In the preoperative CT, there was tracheal stenosis due to enlarged bilateral thyroid lobes and the width of the stenotic lumen was 7mm. Subtotal thyroidectomy improved the dyspnea. Postoperative histopathologic examination confirmed follicular adenoma without malignant lesions or chronic thyroiditis. On postoperative CT, the tracheal stenosis had improved and the lumen had increased to 15mm. The above findings would suggest that it should be keep in mind that even benign thyroid tumors with tracheal stenosis of less than 7mm in the lumen have the possibility of causing dyspnea.

Raman Spectroscopy Discloses Altered Molecular Profile in Thyroid Adenomas.

Follicular patterned nodules are sometimes complex to be classified due to ambiguous nuclear features and/or questionable capsular or vascular invasion. In this setting, there is a poor inter-observer concordance even among expert pathologists. Raman spectroscopy was recently used to separate benign and malignant thyroid nodules based on their molecular fingerprint; anyway, some histologically proved follicular adenomas were clustered as having a characteristic profile of malignant lesions. In this study, we analyzed five follicular thyroid adenomas with a malignant spectroscopic profile compared to five follicular adenomas with a benign Raman spectrum in order to assess possible molecular differences between the two groups. Morphological, immunohistochemical, and molecular analyses evidenced expression of malignancy-associated proteins in four out of five malignant clustered adenomas. The remaining malignant clustered adenoma showed a TSHR mutation previously associated with autonomously functioning follicular carcinomas. In conclusion, thyroid follicular adenomas are a group of morphologically benign neoplasms that may have altered the mutational or expression profile; cases of adenomas with altered immunophenotype are recognized as showing a profile associated with malignancy by Raman spectroscopy. This correlation warrants a more extensive evaluation and suggests a potential predictive value of spectroscopic assessment in recognizing characteristics associated with tumor progression in follicular thyroid neoplasms.

Segmentation and classification of thyroid follicular neoplasm using cascaded convolutional neural network

In this paper, we present a segmentation and classification method for thyroid follicular neoplasms based on a combination of the prior-based level set method and deep convolutional neural network. The proposed method aims to discriminate thyroid follicular adenoma (TFA) and follicular thyroid carcinoma (FTC) in ultrasound images. In their appearance, these two kinds of tumours have similar shapes, sizes and contrasts. Therefore, it is difficult for even ultrasound specialists to distinguish them. Because of the complex background in thyroid ultrasound images, before distinguishing TFA and FTC, we need to segment the lesions from the whole image for each patient. The main challenge of segmentation is that the images often have weak edges and heterogeneous regions. The main issue of classification is that the accuracy depends on the features extracted from the segmentation results. To solve these problems, we conduct the two tasks, i.e. segmentation and classification, by a cascaded learning architecture. For segmentation, to obtain more accurate results, we exploit the Res-U-net framework and the prior-based level set method to enhance their respective abilities. Then, the classification network is trained by sharing shallow layers of the segmentation network. Testing the proposed method on real patient data shows that it is able to segment the lesion areas in thyroid ultrasound images with a Dice score of 92.65% and to distinguish TFA and FTC with a classification accuracy of 96.00%.

Current surgical management of follicular thyroid carcinoma

: Follicular thyroid carcinoma (FTC) comprises a heterogenous group of tumors, which divides into subtypes with different malignant potential: minimally invasive (excellent prognosis), encapsulated angioinvasive and widely invasive FTC (higher risk metastasis and recurrence). Numerous clinical risk factors (presence of metastases, advanced patient age, tumor size and others), which can be used to assess FTC aggressiveness, are discussed with regard to the present literature. The definitive characterization of follicular neoplasms depends on postoperative histology, due to the incapability of preoperative imaging, fine-needle aspiration cytology or molecular analysis to clearly distinguish between FTC and benign follicular thyroid adenoma. In this review, treatment strategies for FTC (according to the WHO 2017 classification of endocrine neoplasms) are presented, as recommended by the leading expert societies American Thyroid Association (ATA), British Thyroid Association (BTA), German Society of Endocrine Surgery (CAEK) and European Society of Endocrine Surgery (ESES). Hemithyroidectomy is sufficient in low-risk FTC (capsular invasion only). Thyroidectomy with postoperative radioiodine therapy is recommended for high-risk FTCs (angioinvasion; widely invasive histology). Prophylactic lymphadenectomy is not necessary. Considering clinical risk factors, an individual surgical approach should be chosen, following a stepwise, escalating surgical management with restricted primary resection (hemithyroidectomy) and, if necessary, completion surgery based on the definitive histopathology.

A Novel Nanoproteomic Approach for the Identification of Molecular Targets Associated with Thyroid Tumors.

A thyroid nodule is the most common presentation of thyroid cancer; thus, it is extremely important to differentiate benign from malignant nodules. Within malignant lesions, classification of a thyroid tumor is the primary step in the assessment of the prognosis and selection of treatment. Currently, fine-needle aspiration biopsy (FNAB) is the preoperative test most commonly used for the initial thyroid nodule diagnosis. However, due to some limitations of FNAB, different high-throughput “omics” approaches have emerged that could further support diagnosis based on histopathological patterns. In the present work, formalin-fixed paraffin-embedded (FFPE) tissue specimens from normal (non-neoplastic) thyroid (normal controls (NCs)), benign tumors (follicular thyroid adenomas (FTAs)), and some common types of well-differentiated thyroid carcinoma (follicular thyroid carcinomas (FTCs), conventional or classical papillary thyroid carcinomas (CV-PTCs), and the follicular variant of papillary thyroid carcinomas (FV-PTCs)) were analyzed. For the first time, FFPE thyroid samples were deparaffinized using an easy, fast, and non-toxic method. Protein extracts from thyroid tissue samples were analyzed using a nanoparticle-assisted proteomics approach combined with shotgun LC-MS/MS. The differentially regulated proteins found to be specific for the FTA, FTC, CV-PTC, and FV-PTC subtypes were analyzed with the bioinformatic tools STRING and PANTHER showing a profile of proteins implicated in the thyroid cancer metabolic reprogramming, cancer progression, and metastasis. These proteins represent a new source of potential molecular targets related to thyroid tumors.

Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses.

Cytologic diagnosis of thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma (FACHAC) is challenging due to cytomorphologic features that overlap with other follicular-patterned lesions. This study was designed to analyze diagnostic categories (DCs) of preoperative fine needle aspiration cytology (FNAC) of histologically proven thyroid FACHACs to evaluate under- or misdiagnoses in FNAC and elucidate potential causes for such phenomena. A total of 104 thyroid nodules with preoperative FNAC which were diagnosed as FACHAC in resection specimens were included in this study. Of these, 66 cases had also undergone thyroid core needle biopsy (CNB); FNAC and CNB DCs were compared in these cases. Various cytologic and histologic parameters were compared between the nodules with different FNAC DCs. After a review of FNAC slides, DCs were re-assigned in 20 (19.2%) out of the 104 cases. Of the 66 cases with CNB diagnoses which were mostly classified as lower DCs in FNAC, 31 (47.0%) were diagnosed as suspicious for a follicular neoplasm in CNB. Cases which were underdiagnosed in FNACs were associated with lower cellularity, predominant macrofollicular pattern, absence of microfollicles arranged in trabecular pattern, and absence of transgressing vessels in cytology smears. High cellularity, microfollicles arranged in trabecular pattern, nucleolar prominence, and large cell dysplasia were more frequently found in malignancy than in benign neoplasm. In conclusion, thyroid FACHACs seem to be under- and misdiagnosed in preoperative FNAC. Innate characteristics of the nodules were associated with under-diagnosis as well as the quality of the FNAC specimens. Certain cytomorphologic features can be helpful in differentiating malignancy among FACHACs.

S1844 Early Onset Colorectal Cancer (EOCRC) in a 43-Year-Old Woman: Current Guidelines Miss Patients at Risk for EOCRC

INTRODUCTION: The incidence of colorectal cancer (CRC) among individuals less than 50 years old is increasing and is estimated to double by 2030. Risk factors for early onset CRC (EOCRC), outside of hereditary CRC syndromes or personal history of IBD, are not well understood. We present a case of EOCRC in a 43-year-old woman. CASE DESCRIPTION/METHODS: The patient presented with six months of worsening hematochezia, abdominal pain, and constipation. Her past medical history included cervical dysplasia status post loop electrosurgical excision and thyroid follicular adenoma status post thyroid lobectomy. Her family history was significant for CRC in her father, diagnosed at age 80. CT abdomen/pelvis showed circumferential rectal wall thickening and prominent perirectal lymph nodes. Colonoscopy revealed a partially obstructing 3cm rectal tumor with associated severe stenosis that was only traversed with an EGD scope. Pathology showed colonic mucosa with high-grade dysplasia. A staging CT chest did not reveal metastases. Her clinical picture was suspicious for colorectal cancer and colorectal surgery recommended neoadjuvant chemotherapy followed by low anterior resection with diverting loop ileostomy. DISCUSSION: This patient's presentation was typical of EOCRC, which tends to present with left-sided disease and in patients older than 40 years. Her risk factor was a family history of CRC in her father; although, he was diagnosed at age 80 at an index colonoscopy. A family history of CRC, even in second- or third-degree relatives, has been associated with increased risk. Some studies have suggested that BMI, tobacco use, coronary artery disease, hypertension, stroke, diabetes, and socioeconomic status are risk factors for EOCRC. Other research indicates that combinations of age, male sex, personal history of IBD, or African American or Asian race are risk factors. Our current U.S. Preventive Services Task Force guidelines do not account for EOCRC. It is difficult to balance the cost effectiveness of initiating the American Cancer Society qualified recommendation to start screening at age 45 versus increasing screening rates and diagnostic colonoscopy completion rates among patients over age 50. As evidenced by our patient, simply lowering the screening age may not be an effective intervention to capture EOCRC phenotypes. Further research is needed to improve understanding of the associated biological and environmental risk factors to improve early identification of individuals at high risk for EOCRC.Figure 1.: Partially-obstructing rectal tumor prior to biopsy.

Classification of Thyroid Tumors Based on Mass Spectrometry Imaging of Tissue Microarrays; a Single-Pixel Approach.

The primary diagnosis of thyroid tumors based on histopathological patterns can be ambiguous in some cases, so proper classification of thyroid diseases might be improved if molecular biomarkers support cytological and histological assessment. In this work, tissue microarrays representative for major types of thyroid malignancies—papillary thyroid cancer (classical and follicular variant), follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer—and benign thyroid follicular adenoma and normal thyroid were analyzed by mass spectrometry imaging (MSI), and then different computation approaches were implemented to test the suitability of the registered profiles of tryptic peptides for tumor classification. Molecular similarity among all seven types of thyroid specimens was estimated, and multicomponent classifiers were built for sample classification using individual MSI spectra that corresponded to small clusters of cells. Moreover, MSI components showing the most significant differences in abundance between the compared types of tissues detected and their putative identity were established by annotation with fragments of proteins identified by liquid chromatography-tandem mass spectrometry in corresponding tissue lysates. In general, high accuracy of sample classification was associated with low inter-tissue similarity index and a high number of components with significant differences in abundance between the tissues. Particularly, high molecular similarity was noted between three types of tumors with follicular morphology (adenoma, follicular cancer, and follicular variant of papillary cancer), whose differentiation represented the major classification problem in our dataset. However, low level of the intra-tissue heterogeneity increased the accuracy of classification despite high inter-tissue similarity (which was exemplified by normal thyroid and benign adenoma). We compared classifiers based on all detected MSI components (n = 1536) and the subset of the most abundant components (n = 147). Despite relatively higher contribution of components with significantly different abundance and lower overall inter-tissue similarity in the latter case, the precision of classification was generally higher using all MSI components. Moreover, the classification model based on individual spectra (a single-pixel approach) outperformed the model based on mean spectra of tissue cores. Our result confirmed the high feasibility of MSI-based approaches to multi-class detection of cancer types and proved the good performance of sample classification based on individual spectra (molecular image pixels) that overcame problems related to small amounts of heterogeneous material, which limit the applicability of classical proteomics.

Weight of Evidence and Human Relevance Evaluation of the Benfluralin Mode of Action in Rats (Part II): Thyroid carcinogenesis

Benfluralin is an herbicide of the dinitroaniline class used to control grasses and weeds. In a 2 year dietary study in rats, benfluralin increased incidences of thyroid follicular adenoma and carcinoma at high dietary concentrations (≥2500 ppm). The benfluralin toxicology database suggests the mode of action (MOA) is initiated by induction of liver metabolizing enzymes, particularly thyroid hormone specific UGTs, a major pathway for T4 clearance in rats. As reported with phenobarbital, this effect triggers negative feedback regulation, increasing thyroid stimulating hormone (TSH) release into circulating blood. When sustained over time, this leads to thyroid changes such as follicular hypertrophy, hyperplasia and thyroid follicular tumors with chronic exposures. The described MOA was previously established in rat studies with various chemical activators of xenobiotic receptors in the liver. It is generally considered as non-relevant in humans, due to differences between humans and rats in T4 turnover and susceptibility to this carcinogenic MOA. A structured methodology based on the IPCS/MOA/Human Relevance framework was used in the evaluation of available benfluralin data, and the conclusion was determined that the carcinogenic potential of benfluralin in the thyroid is not relevant in humans.

Comprehensive Assessment of TERT mRNA Expression across a Large Cohort of Benign and Malignant Thyroid Tumours.

The presence of TERT promoter (TERTp) mutations in thyroid cancer have been associated with worse prognosis features, whereas the extent and meaning of the expression and activation of TERT in thyroid tumours is still largely unknown. We analysed frozen samples from a series of benign and malignant thyroid tumours, displaying non-aggressive features and low mutational burden in order to evaluate the presence of TERTp mutations and TERT mRNA expression in these settings. In this series, TERTp mutations were found in 2%, only in malignant cases, in larger cancers, and from older patients. TERT mRNA expression was detected in both benign and malignant tumours, with increased frequencies in the malignant tumours with aggressive histotypes, larger tumours, and from older patients. In benign tumours, TERT mRNA expression was found in 17% of the follicular thyroid adenoma (FTA) with increased levels of expression in smaller tumours and associated with the presence of thyroiditis. TERTp mutations and TERT mRNA expression are correlated with worse prognosis features in malignant thyroid tumours, whereas TERT mRNA expression in the benign tumours is associated with the presence of thyroiditis.

Analysis of Thyroid Cases in a Teaching Hospital

Background: Hyperthyroidism, hypothyroidism, inflammation of thyroid (thyroiditis), thyroid enlargement (goitre), thyroid nodules and thyroid cancer are amongst the thyroid disorders. The study aims to the occurrence of various post-operative complications following thyroidectomy. Subjects and Methods: One hundred patients who underwent thyroid surgery, for various thyroid disorders were taken for the study. elaborate analysis of those patients who underwent thyroidectomy was done relating to numerous aspects like age, sex, diagnosis & indication for surgery, type of thyroidectomy procedure done, incidence of individual complications. Results: About 37% of the patients were diagnosed with multinodular goiter,followed in frequency by solitary thyroid nodule (27%) and Follicular adenoma (11%). Malignancy(bothfollicular in 3 patientsandpapillary in 7 patients) was diagnosed in total 10 Patients out of 100. Three cases each of Diffuse colloid goiter and Primary thyrotoxicosis. Conclusion: Careful assessment of surgical and medical thérapeutic methods can still minimize the complications and repetition of thyroid surgery.

Causative role for defective expression of mitochondria-eating protein in accumulation of mitochondria in thyroid oncocytic cell tumors.

Oncocytic cell tumor of the thyroid is composed of large polygonal cells with eosinophilic cytoplasm that is rich in mitochondria. These tumors frequently have the mutations in mitochondrial DNA encoding the mitochondrial electron transport system complex I. However, the mechanism for accumulation of abnormal mitochondria is unknown. A noncanonical mitophagy system has recently been identified, and mitochondria‐eating protein (MIEAP) plays a key role in this system. We therefore hypothesized that accumulation of abnormal mitochondria could be attributed to defective MIEAP expression in these tumors. We first show that MIEAP was expressed in all the conventional thyroid follicular adenomas (FAs)/adenomatous goiters (AGs) but not in oncocytic FAs/AGs; its expression was defective not only in oncocytic thyroid cancers but also in the majority of conventional thyroid cancers. Expression of MIEAP was not correlated with methylation status of the 5′‐UTR of the gene. Our functional analysis showed that exogenously induced MIEAP, but not PARK2, reduced the amounts of abnormal mitochondria, as indicated by decreased reactive oxygen species levels, mitochondrial DNA / nuclear DNA ratios, and cytoplasmic acidification. Therefore, together with previous studies showing that impaired mitochondrial function triggers compensatory mitochondrial biogenesis that causes an increase in the amounts of mitochondria, we conclude that, in oncocytic cell tumors of the thyroid, increased abnormal mitochondria cannot be efficiently eliminated because of a loss of MIEAP expression, ie impaired MIEAP‐mediated noncanonical mitophagy.

Significance of Insulin-Like Growth Factor II Mrna-Binding Protein 3 (IMP3) Expression in Selected Thyroid Lesions

Background: Differentiation of benign from malignant follicular thyroid lesions remains difficult and the ability of molecular markers to differentiate between them still unclear. The aim of this study was to evaluate the usefulness of IMP3 expression to distinguish benign from malignant thyroid lesions. Methods: This is a retrospective study upon selected 57 thyroid lesions designated as; 7 cases of Hashimoto thyroiditis (HT), 10 cases of hyperplastic nodules (HN), 15 cases of follicular thyroid adenoma (FTA), 13 cases of conventional papillary thyroid carcinoma (PTC), 6 cases of follicular variant of papillary thyroid carcinoma (FV-PTC), and 6 cases of follicular thyroid carcinoma (FTC). Immunohistochemistry was applied on formalin-fixed, paraffin-embeded tissue blocks using IMP3. clinicopathological data were reviewed from patients' pathological reports and correlated with IMP3 expression. Results: IMP3 positivity was seen in1/7 cases (14.3%) of HT, 2/10 cases (20%) of HN, 4/15 cases (26.7%) of FTA, 12/13 cases of PTC, and in all (100%) FV-PTC & FTC cases. IMP3 staining was significantly increased from normal thyroid tissue up to malignant tumors (P<0.01). IMP3 showed 96% sensitivity and 78.1% specificity for malignant tumors. IMP3 expression was positively correlated with grade and tumor size in malignant cases (P<0.05). No significant correlation was found in IMP3 expression with patient age, sex, capsular invasion, lymphatic/vascular invasion, lymph node metastasis, distant metastasis and TNM stage. Conclusions: IMP3 is a potential diagnostic marker for thyroid cancer and can be a promising marker for distinguishing benign from malignant follicular patterned thyroid lesions.

NPAsym: an open-source plugin for ImageJ to quantify nuclear shape asymmetry

Background and objectives: The nucleus is a complex and dynamic organelle enclosing the major part of the cell's genome. A growing body of evidence suggests that changes in the shape of this organelle can influence cell activities. The other way around, altered nuclear shape may be indicative of impaired cell function. Symmetry is an important aspect of nuclear shape not receiving the attention it merits. We address this problem by presenting a software tool allowing to quantify nuclear shape asymmetry in light microscopy images. Methods: The software named nPAsym is written in Scala and implemented as a plugin to ImageJ making possible to use it in combination with other ImageJ tools. The plugin works with 8-bit images segmented into black nuclear masks and white background. It performs a number of operations allowing to analyze multiple objects within a single image, removing some segmentation artefacts, filtering out objects incomplete and below a specified size. The feature of interest is quantified using the notion of point asymmetry. The performance of nPAsym was tested in a small-scale study comparing nuclear shapes for cells of nodular goiter, follicular thyroid adenoma and papillary thyroid carcinoma. Results: We present nPAsym, the ImageJ plugin, that measures nuclear shape asymmetry. It works with digital microscopic images segmented using either a raster graphics editor or built-in ImageJ functions. nPAsym is packaged in a single .jar file and does not require installation as well as configuration. It has proved effective in distinguishing between some of the nuclear shape phenotypes. Conclusions: nPAsym is the user-friendly, platform-independent and open-source software tool allowing to quantify nuclear shape asymmetry in digital images captured from cytologic and histologic preparations. It has a potential to become useful for both experimental research and diagnostics.

Role of miR‐155‐5p expression and its involvement in apoptosis‐related factors in thyroid follicular carcinoma

Thyroid follicular carcinoma is a malignant tumor from thyroid follicular epithelium, which is prone to involve capsular and vascular invasion. The present study was conducted in order to detect the expression of microRNA-155-5p (miR-155-5p) in thyroid follicular carcinoma with an attempt to analyze its involvement in apoptosis-related factors. Forty-five patients with thyroid follicular carcinoma made up the observation group and 45 patients with thyroid follicular adenoma were included into the control group. Tissues of thyroid follicular carcinoma and thyroid follicular adenoma were obtained from the patients, and analysed for expression of miR-155-5p by real-time fluorescence quantitative PCR (qPCR). The expression of cysteine-containing aspartic acid protein hydrolase-3 (Caspase-3) in thyroid follicular carcinoma was detected with the use of Western Blot analyses. Immunohistochemical method was used to detect the expression of B-cell lymphoma protein-2 (Bcl-2) in thyroid follicular carcinoma. There was significant difference in the expression of miR-155-5p between the two groups (Observation vs Control: 1.46±0.42 vs 0.98±0.33 P<.05). The expression of miR-155-5p was significantly different in the maximum diameter of tumor, vascular invasion and neural invasion (maximum diameter of tumor <4cm vs ≥4cm: 1.36±0.40 vs 1.68±0.32, vascular invasion N vs Y: 1.35±0.42 vs 1.69±0.39, Neural invasion N vs Y: 1.35±0.38 vs 1.70±0.31 P<.05). However, there was no significant difference in the expression of miR-155-5p in terms of different gender, age and group with or without lymph node metastasis (P>.05). Based on survival analysis, patients with high expression of miR-155-5p experienced short survival time (median survival time was 45months, P<.05). There was a negative correlation between miR-155-5p and Caspase-3 (r=-.50, P<.05). In addition, positive correlation was observed between miR-155-5p and Bcl-2 (r=.55, P<.05). There was increased expression of miR-155-5p in thyroid follicular carcinoma. The abnormal expression of miR-155-5p may be an independent prognostic factor for thyroid follicular carcinoma associated with cell apoptosis.