Anna Cyniak-Magierska

COX-2 expression in papillary thyroid carcinoma (PTC) in cytological material obtained by fine needle aspiration biopsy (FNAB).

BackgroundCOX-2 is an enzyme isoform that catalyses the formation of prostanoids from arachidonic acid. An increased COX-2 gene expression is believed to participate in carcinogenesis. Recent studies have shown that COX-2 up-regulation is associated with the development of numerous neoplasms, including skin, colorectal, breast, lung, stomach, pancreas and liver cancers. COX-2 products stimulate endothelial cell proliferation and their overexpression has been demonstrated to be involved in the mechanism of decreased resistance to apoptosis. Suppressed angiogenesis was found in experimental animal studies as a consequence of null mutation of COX-2 gene in mice. Despite the role of COX-2 expression remains a subject of numerous studies, its participation in carcinogenesis or the thyroid cancer progression remains unclear.MethodsTwenty three (23) patients with cytological diagnosis of PTC were evaluated. After FNAB examination, the needle was washed out with a lysis buffer and the obtained material was used for COX-2 expression estimation. Total RNA was isolated (RNeasy Micro Kit), and RT reactions were performed. β-actin was used as endogenous control. Relative COX-2 expression was assessed in real-time PCR reactions by an ABI PRISM 7500 Sequence Detection System, using the ΔΔCT method.ResultsCOX-2 gene expression was higher in patients with PTC, when compared to specimens from patients with non-toxic nodular goitre (NTG).ConclusionsThe preliminary results may indicate COX-2 role in thyroid cancer pathogenesis, however the observed variability in results among particular subjects requires additional clinical data and tumor progression analysis.

The role of phosphoinositide 3-kinase subunits in chronic thyroiditis

BackgroundThe risk of neoplastic transformation in patients with chronic thyroiditis (Hashimoto’s thyroiditis – HT) is slightly increased. Genetic background of this observation is still unclear. PI3K isoforms are linked with inflammatory and neoplastic processes, thus they appear to be interesting subjects of a research in this respect. The aim of our study was to assess the PIK3CA, PIK3CB, PIK3CD and PIK3CG genes expression levels in HT.MethodsFollowing conventional cytological examination, 67 thyroid FNAB specimens, received from patients with HT, were quantitatively evaluated regarding PIK3CA, PIK3CB, PIK3CD and PIK3CG expression levels by real-time PCR in the ABI PRISM ®7500 Sequence Detection System.ResultsThe performed analysis has revealed significantly higher expression levels (RQ) of PIK3CD, PIK3CG and PIK3CA genes in comparison with PIK3CB gene (p<0.05) and significantly higher gene expression level of PIK3CD in comparison with PIK3CA (p<0.05).ConclusionThe observed increased PIK3CD, PIK3CG genes expression in HT is probably related to lymphocyte infiltration commonly seen in this condition, however, the role of increased PIK3CA gene expression in the multi-step carcinogenesis process cannot be excluded.

Cognitive Function, APOE Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Background: The objective of the study was to analyze a potential association between cognitive functions and thyroid status in postmenopausal women with different polymorphisms of the apolipoprotein E gene (APOE). Methods: The examined population included 402 postmenopausal women from south-eastern Poland. The evaluation of cognitive functions was made with the use of the diagnostic Central Nervous System-Vital Signs equipment (Polish version). Multiplex polymerase chain reactions were performed to assess APOE polymorphisms. The thyroid hormone tests were assessed by an accredited laboratory. Results and Conclusion: Lower results of cognitive functions were associated with the presence of the ε4 APOE allele in postmenopausal women. The ε4 APOE polymorphism was associated with a higher concentration of thyroid-stimulating hormone and lower concentrations of free triiodothyronine and total triiodothyronine.

Patterns of cyclin A and B1 immunostaining in papillary thyroid carcinoma

INTRODUCTION AND OBJECTIVES Cyclin A, encoded by CCNA (cyclin A) gene with locus in chromosome 4q27, and cyclin B1, encoded by CCNB1 (cyclin B1) gene with locus in chromosome 5q12, are proteins that play a key role in the passage through the restriction point in G2 phase of the cell cycle. The aim of the study was to analyse immunohistochemically the expression of cyclins A and B1 in different variants of papillary thyroid carcinoma (PTC). MATERIAL AND METHODS The immunostaining patterns of the proteins in question in the tissue of 40 resected PTC (20 cases of classic variant of PTC, 9 cases of PTC follicular variant and 11 cases of other non-classic variants of PTC) were investigated. RESULTS On analyzing cyclin A and B1 expression, positive staining in 90% cases of PTC were observed. The study revealed a significant difference in expression of cyclins A and B1 between classic and non-classic variants of PTC. The expression of both examined cyclins was weaker in the classic variant of PTC. In the group of follicular variant of PTC, the expression of cyclins was of medium intensity and in the group of other non-classic variants of PTC, the expression was clearly higher. CONCLUSIONS The results of the presented study suggest that cyclins A and B1 expression may have a characteristic pattern of immunostaining for particular variants of PTC. If the obtained results are confirmed in a larger group of patients, the diagnostic panel constructed of the antibodies against these proteins may increase the diagnostic accuracy in PTC cases.

The syndromes of reduced sensitivity to thyroid hormone – the current state of art

The clinical, laboratory, genetic and molecular characteristics of syndromes of reduced sensitivity to thyroid hormone are the subject of this abstract. The syndrome of reduced sensitivity to thyroid hormone in the majority of cases is caused by point mutations in the thyroid hormone receptor β (TRβ) gene. Before TRβ gene mutations were recognized, resistance to thyroid hormone (RTH) was subdivided on clinical basis into generalized, isolated pituitary and peripheral tissue. Nowadays this classification has a clinical usefulness, but it seems to have no logical etiologic grounds. The mutations in TRβ gene have been found in over 3000 individuals belonging to approximately 1000 families. While the clinical presentation is variable, the main features are: high serum FT4 and usually also FT3 concentrations, non-suppressed – sometimes slightly elevated serum thyrotropin (TSH), commonly a goiter. The majority of subjects have a near normal metabolic state, sometimes coexistence of clinical symptoms of thyroid hormones deficiency and excess takes place in one patient. Thus, delayed growth and bone maturation, and learning disabilities can be present along with hyperactive behavior and sinus tachycardia. Mental retardation was found in 3% of cases. Attention deficit hyperactivity disorder (ADHD) is also present in about half of patients with RTH syndrome. In 15% of families with RTH symptoms no mutations in the TRβ gene were found. The term nonTR-RTH refers to this subgroup of individuals, clinically and biochemically identical with RTH caused by TRβ mutations. Recently, mutations in TRα1 gene have been described in two families. First nonsense mutation produces a truncated TRα1 (E403X) that lacks the C-terminal α-helix. It has been identified in a 6 year-old girl with chronic constipation, and growth and developmental delay. Another family with TRα1 gene mutation was described in 2012. In both cases, thyroid function tests were distinct from those in classical RTH with TRβ gene mutations. These patients had low serum T4, high T3, and very low rT3. Two relatively novel syndromes presenting reduced sensitivity to thyroid hormone: membrane transport defect and thyroid hormone metabolism defect were described. This led to the broadening of the definition of reduced sensitivity to thyroid hormone to encompass all the defects that can interfere with the biological activity of a chemically intact hormone, secreted in normal amounts. Thyroid hormone cell membrane transporter defect (THCMTD) is caused by mutations in the MCT8 gene. It is an X-linked defect. Mutations have 100% penetrance in males who manifest both neuropsychomotor impairment and characteristic thyroid test abnormalities (high serum T3, low rT3, low normal or reduced T4 with slightly elevated TSH level). The defect of the intracellular metabolism of thyroid hormones (THMD) is caused by mutations in the SECISBP2 gene who is required for the synthesis of selenoproteins, including thyroid hormone deiodinases. It was described in 10 patients from 8 families.