Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy * genetika patologie MeSH
- mikro RNA * genetika MeSH
- mutace * MeSH
- nádorové biomarkery genetika MeSH
- nádory štítné žlázy * genetika patologie MeSH
- papilární karcinom štítné žlázy * genetika patologie MeSH
- protoonkogenní proteiny B-Raf * genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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Příručka a učebnice obsahující testy z biologie vhodné k přípravě ke zkouškám na vysokou školu. Určeno studentům středních škol.
- Konspekt
- Biologické vědy
- Učební osnovy. Vyučovací předměty. Učebnice
- NLK Obory
- biologie
- NLK Publikační typ
- učebnice středních škol
- testy
BACKGROUND: A low-risk thyroid tumour, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced in 2016. NIFTP criteria require a thorough histological examination to rule out capsular and lymphovascular invasion, which denies the possibility of preoperative cytological diagnosis. Nevertheless, since the adoption of the new entity, the cytology of NIFTP has been a subject of interest. OBJECTIVES: The present systematic review and meta-analysis investigate the cytological diagnosis of NIFTP. METHOD: An online PubMed literature search was conducted between March 1, 2020, and June 30, 2020, for all original articles considering the cytology of histologically proven NIFTP. The studies including data on fine needle aspiration specimens classified by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) categories, risk of malignancy (ROMs) in the TBSRTC categories, and cytomorphological features of NIFTP were included in the meta-analysis. Non-English studies and case reports were excluded. The data were tabulated and statistical analysis was performed with Open Meta-Analyst program. RESULTS: Fifty-eight studies with a total of 2,553 NIFTP cases were included in the study. The pooled prevalence of NIFTP cases was calculated among 25,892 surgically resected cases from 20 studies and the results show that NIFTP consisted 4.4% (95% confidence interval [CI]: 3.5-5.4%) of all cases. Most of the NIFTP cases (79.0%) belonged to the intermediate categories of TBSRTC. The pooled distribution of NIFTP cases in each TBSRTC category was 1.3% (95% CI: 0.8-1.7%) in non-diagnostic (ND), 8.9% (95% CI: 6.9-10.8%) in benign, 29.2% (95% CI: 25.0-33.4%) in atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 24.2% (95% CI: 19.6-28.9%) in follicular neoplasm (FN), 19.5% (95% CI: 16.1-22.9%) in suspicious for malignancy (SM), and 6.9% (95% CI: 5.2-8.7%) in malignant. Compared to pre-NIFTP era, the pooled risk differences of ROM were reduced by 2.4% in ND, 2.7% in benign, 8.2% in AUS/FLUS, 8.2% in FN, 7.3% in SM, and 1.1% in the malignant category. The cytomorphological features of NIFTP were similar to follicular variant of papillary thyroid carcinoma (FVPTC) but lesser to papillary thyroid carcinoma (PTC). CONCLUSIONS: Based on our results, NIFTP remains a histological diagnosis. Although cytomorphological features cannot be used in differentiating NIFTP from FVPTC, they may guide in separating NIFTP from PTC. Features such as papillae, microfollicles, giant cells, psammoma bodies, and the amount of papillary-like nuclear features should be taken into account when suspicious of NIFTP. NIFTP should not have papillae or psammoma bodies, and giant cells were rarely observed.
Programmed cell death ligand (PD-L1)/PD-1 expression has been studied in a variety of cancers and blockage of PD-L1/PD-1 pathway is a cornerstone of immunotherapy. We studied PD-L1/PD-1 immunohistochemical expression in 47 thyroid gland specimens in groups of (1) Hashimoto thyroiditis (HT) only; (2) HT and follicular epithelial dysplasia (FED); and (3) HT, FED, and papillary thyroid carcinoma (PTC). PD-1 positivity was found in immune cells, namely in lymphocytes, macrophages, and plasma cells with mean values for lymphocytes and macrophages 9% in HT group, 4% in FED group, and 4% in PTC group. PD-L1 positivity was identified in both immune cells and in the normal epithelial cells. In the HT group, mean PD-L1 staining on immune cells was 6%, in FED group 5%, and in PTC group 7%. The mean PD-L1 staining on the epithelial cells in the inflammatory parenchyma was 11.7% in HT, 13.4% in FED, and 8.3% in PTC group. The mean PD-L1 staining of FED foci was 47.2% in FED group and 33.6% in PTC group. The mean tumor proportion score (TPS) was 10.4%, and the mean combined positive score (CPS) was 15.5. At the moment, PTC is not a target of immunotherapy. However, understanding the complex issue of concurrent inflammation and autoimmunity can importantly influence the cancer treatment in future.
Since Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) was introduced as a new thyroid tumour entity, many studies, and meta-analyses on diagnosing NIFTP have been published. NIFTP-revised histopathological criteria emerged in 2018. NIFTP is defined as a histological entity and its diagnosis requires a careful histological examination. Its molecular profile is similar to follicular-like tumours. Ultrasound features are unable to differentiate NIFTP. NIFTP is not a cytological diagnosis, but it influences the risk of malignancy in several categories of The Bethesda System for Reporting Thyroid Cytopathology terminology.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Follicular epithelial dysplasia (FED) is described as Hashimoto thyroiditis-related atypia and is thought to be a possible precancerous lesion. Dysplasia as an interface between normal state and carcinoma is described in a wide range of diseases and carcinogenesis chains. On the other hand, inflammation-related atypia and cancerogenesis is also widely studied. In this study, we retrospectively analyzed 91 specimens of thyroid gland surgical resections with FED during a 10-year-period at the university hospital pathology department. The study population consisted of 68 females and 15 males aged between 22 and 86 years. The preoperative cytology diagnoses had mainly been in the indeterminate categories with prevailing AUS/FLUS results in the FED-only group (p = 0.005) and suspicious for malignancy and malignant in the group with FED plus adjacent malignancy. The decision for surgery was malignancy related in 48.2% of the cases. The lesions were sized 0.1-3.5 mm and multifocal in 45.1% of the cases. Immunohistochemically, the atypical cells were cyclin D1-positive in 67.5%, galectin-3 in 72.7%, CK19 in 85.7%, and HBME-1 in 87.0% of cases. In conclusion, FED is suggested to be a pathogenetic link between inflammation-related atypia and papillary carcinoma and thus a premalignant precursor of papillary carcinoma in HT as 36.1% of the specimens contained also papillary carcinoma in the present study. Both histopathological nuclear features and the immunoprofile of FED are widely shared with that of papillary carcinoma.
- MeSH
- dospělí MeSH
- Hashimotova nemoc komplikace patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory štítné žlázy etiologie patologie MeSH
- prekancerózy etiologie patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- štítná žláza patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Thyroid cytology is a widely accepted tool in the clinical triaging of nodular lesions. Cell blocks (CBs) can help in the diagnosis of atypical lesions, namely, thyroid Bethesda category of Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). METHODS: In a series of 224 AUS/FLUS thyroid samples with CB, we studied CB cellularity and feasibility of 3 immunohistochemical markers (cytokeratin 19 [CK19], HBME-1, and galectin-3) apart and in combination. RESULTS: The CBs were non-diagnostic in 34 cases. Twenty-four CBs contained <10 cells, 45 CBs 10-50 cells, and 121 CBs >50 cells. Notably, more cellularity was found in CBs performed by plasma-thrombin and in-house techniques (p < 0.001). The diagnostic accuracy to detect malignancy was 65.1% for CK19, 72.1% for HBME-1, and 70.3% for galectin-3. CONCLUSION: In conclusion, CB cellularity is essential for successful immunohistochemistry application and further diagnostic workup of AUS/FLUS cases.
- MeSH
- fixace tkání MeSH
- galektiny analýza MeSH
- imunohistochemie * MeSH
- keratin-19 analýza MeSH
- krevní proteiny analýza MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory štítné žlázy chemie patologie MeSH
- prediktivní hodnota testů MeSH
- reprodukovatelnost výsledků MeSH
- retrospektivní studie MeSH
- studie proveditelnosti MeSH
- stupeň nádoru MeSH
- zalévání tkání do parafínu * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- diagnóza stomatologická MeSH
- lidé MeSH
- nádory příušní žlázy * diagnóza MeSH
- parotis * chirurgie MeSH
- senzitivita a specificita MeSH
- tenkojehlová biopsie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
MiR-34a belongs to the class of small non-coding regulatory RNAs and functions as a tumor suppressor. Under physiological conditions, miR-34a has an inhibitory effect on all processes related to cell proliferation by targeting many proto-oncogenes and silencing them on the post-transcriptional level. However, deregulation of miR-34a was shown to play important roles in tumorigenesis and processes associated with cancer progression, such as tumor-associated epithelial-mesenchymal transition, invasion, and metastasis. Moreover, further understanding of miR-34a molecular mechanisms in cancer are indispensable for the development of effective diagnosis and treatments. In this review, we summarized the current knowledge on miR-34a functions in human disease with an emphasis on its regulation and dysregulation, its role in human cancer, specifically head and neck squamous carcinoma and thyroid cancer, and emerging role as a disease diagnostic and prognostic biomarker and the novel therapeutic target in oncology.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Despite the interest of researchers in IgG4-related disease (IgG4-RD), many questions still remain unanswered regarding the thyroid gland. We aimed to clarify the relationship between IgG4-positive plasma cells and the histopathological pattern in the Hashimoto thyroiditis (HT) in a Finnish series. HT specimens (n = 280) were retrieved from the Department of Pathology, Fimlab Laboratories. After re-evaluation, 82 (29%) cases (72 females and 10 males, 52 ± 17 years) with significant fibrosis were selected. CD38, IgG and IgG4 positivity in plasma cells was evaluated by immunohistochemistry. Adjusted IgG4-positive plasma cells per HPF > 20 and IgG4- to IgG-positive plasma cell ratio > 30% were adopted as threshold criteria and related to other morphological features. IgG4-positive HT group included 13 cases (15% from fibrotic HT, 4.6% from all HT, 50 ± 15 years, 11 females) with adjusted HPF count 30 ± 5 (23-40) IgG4-positive cells. IgG4-positivity significantly correlated with the presence of lobulation, oncocytic metaplasia and certain type of fibrosis, fibrosis spread outside the gland, lymphocytes/plasma cells epithelial penetration, the predominance of microfollicles and follicular atrophy in the present study. Despite the persisting uncertainty whether HT is IgG4-RD, HT with IgG4-positive plasma cells is histopathologically distinct entity with some geographic variability.
- MeSH
- antigeny CD38 metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- fibróza MeSH
- Hashimotova nemoc imunologie patologie MeSH
- imunoglobulin G metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny metabolismus MeSH
- mladiství MeSH
- mladý dospělý MeSH
- plazmatické buňky metabolismus patologie MeSH
- počet lymfocytů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- štítná žláza imunologie patologie MeSH
- zánět MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Finsko MeSH
