Katarzyna Wojciechowska-Durczynska

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.

Assessment of cyclooxygenase-1 and 2 gene expression levels in chronic autoimmune thyroiditis, papillary thyroid carcinoma and nontoxic nodular goitre

IntroductionThe cyclooxygenases are a group of enzymes catalyzing the formation of prostaglandins from arachidonic acid. Cyclooxygenase-1 (COX-1) is a constitutive form, thought to be a “housekeeping gene”, with constant levels of expression in most tissues. COX-1 expression in the thyroid gland, except for medullary thyroid carcinoma, has not been a subject of much interest. Cyclooxygenase-2 (COX-2) can be expressed in response to various stimuli, such as mitogens, hormones, cytokines, growth factors. The product of COX-2 activity has been implicated in carcinogenesis.Recent studies have shown that up-regulation of COX-2 is associated with numerous neoplasms. Hereby, we present a study analysing COX-1 and COX-2 expression in papillary thyroid carcinoma (PTC), Hashimoto thyroiditis (HT) and nontoxic nodular goitre (NNG) in fine needle aspiration biopsy (FNAB) washouts and in postoperative tissue.Material and methodsCytological specimens from 120 patients (105 females and 15 males) have been studied, including patients with HT, PTC and NNG. Moreover, we have examined postoperative tissue specimens from 51 patients with PTC and NNG.The methods of molecular analysis have included extraction of total RNA from FNAB cytological material and postoperative tissues, spectrophotometric assessment of the RNA purity, cDNA synthesis in reverse transcription reaction and an analysis of genes expression data by real-time PCR.ResultsThe performed analysis has revealed statistically significant higher expression level of the COX-2 gene in PTC group, in comparison with HT and NNG groups (in both cytological and postoperative material).In PTC patients, COX-2 gene expression levels in the material obtained by FNAB were similar to those in the postoperative thyroid tissue.No correlations between COX-2 gene expression level and TNM staging in PTC samples have been observed.There were no correlations between COX-2 expression and anti-TPO antibodies level, or patient’s sex or age in the studied groups. Also, there were no correlations of COX-1 gene expression level among PTC, HT and NNG groups.ConclusionsOur results suggest that COX-2 gene does not participate in the mechanisms involved in molecular association of HT with PTC. However, in case of PTC itself, it may play some role in neoplastic transformation.

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.

Riedel's thyroiditis - a case report with genes' expression studies

BackgroundGenetic background of Riedels thyroiditis remains unknown. Herein, we describe our results of studies on genes expression levels in Riedels thyroiditis.Case report and genetic findingsWe report the case of 48-year old woman with Riedels thyroiditis who has presented unusual course of disease with non-specific cervical discomfort, though as with no pain and/or no compression symptoms. After surgery, thyroid specimens were quantitatively evaluated, regarding PIK3CA, PIK3CD, PIK3CG, Tg, TGFB1, THRB, COL1, CDKN1C, CDH3 and CACNA2D2 genes expression levels, by real-time PCR in the ABI PRISM® 7500 Sequence Detection System. Out of 10 above genes, in 2 cases the expression was higher than in respective Controls of unchanged thyroid tissue. In the remaining 8 cases, expression in question became comparable or lower as in Controls.DiscussionThe association between increased expression levels of PIK3CA and CDH3 genes and Riedels thyroiditis is not well-defined. However, the increased expression of PIK3CA and CDH3 genes in our case report and in previous studies of other authors on various malignancies may suggest possible molecular relation between Riedels thyroiditis and certain neoplastic processes, the relation of which requires further genetic evaluation. It is to be stressed that gene expression studies in Riedels thyroiditis are difficult to perform, mainly due to fibrosis, resulting in scarce thyroid specimens and - in consequence - small amount of genetic material.

The influence of liver and pancreas surgery on the thyroid function

BackgroundNowadays, the increasing number of oncologic patients with liver or pancreatic tumours are subjected to surgical treatment, as it can provide a long-term survival or sometimes cure. As a result, numerous new clinical questions regarding metabolic disturbances in these patients have been arisen. Among others, the impact of the pancreas and liver surgery extent in relation to the thyroid function remains to be elucidated.Materials and methodsThe study comprised 51 patients (25 men and 26 women, mean age ± SD 61.6 ± 10.4 yrs, mean ± SD) with pancreatic or liver tumours, qualified for abdominal operation. Serum levels of FT3, FT4 and TSH were measured on the day before (time “0”) and on the 1st, 3rd and 5th day after surgery in two (2) subgroups reflecting the extent of surgery: twenty seven (27) patients (14 men and 13 women, mean age ± SD 61.5 ± 11.8 yrs) after major surgery (Whipple’s surgery, right and left hemihepatectomy, segmentectomy of the liver, distal pancreatectomy, total duodenopancreatectomy) and twenty four (24) patients (11 men and 13 women, mean age ± SD 61.8 ± 8.9 yrs) after minor, palliative surgery (exploratory laparotomy, gastroenterostomy, triple by-pass, liver tumour embolization, hepaticojejunostomy). Additionally, the obtained results were analyzed in relation to the type of the disease (pancreatic surgery vs liver surgery).ResultsMean serum FT3 level decreased significantly during the study in major and minor surgery subgroups (p<0.001, in both) in comparison to the baseline values, accompanied by stable serum concentrations of TSH (NS) and FT4 (NS). The above decreasing tendency in FT3 concentrations was similar in both subgroups (NS), the same as were unchanged levels of TSH (NS) and FT4 (NS). Mean FT4 concentration on the 3rd and 5th day after major surgery was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.002, p=0.032, respectively). Similarly, mean FT3 concentration on the 3rd day in minor surgery subgroup was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.015).DiscussionOur findings have confirmed essential reduction of FT3 values after abdominal surgery, independently of surgery extent. Additionally, pancreatic tumour patients are more likely to have lower FT3 and FT4 levels after surgery when compared to liver tumour patients.

Relationship between urine lipid peroxidation, anthropometric parameters and parameters associated with goitre formation in school-age children

Introduction Oxidative stress has been implicated in the normal ageing process and the pathogenesis of several diseases, including goitre. The aim of the study was to evaluate the relationship between urine lipid peroxidation (LPO) and anthropometric parameters as well as the parameters associated with goitre formation in children. Material and methods The subjects included 172 healthy children (93 girls and 79 boys) aged 8–15, divided into 4 age groups – group I (8–9 years), group II (10–11 years), group III (12–13 years) and group IV (14–15 years) – and into 2 groups based on the BSA: the BSA-1 group (≤ 0.55 m2) and the BSA-2 group (> 0.55 m2). Results The value of LPO was the highest in group I but the difference between the groups was not statistically significant (p = 0.074). In the BSA-1 group, the LPO was higher than in the BSA-2 group (12.75 ±6.90 nmol/ml and 10.79 ±4.86 nmol/ml, respectively; p = 0.023). We found a weak, negative linear correlation between LPO and age (r = –0.216; p < 0.005), body mass (r = –0.153; p < 0.05), height (r = –0.152; p < 0.05) and BSA (r = –0.151; p < 0.05). Conclusions Anthropometric parameters of school-age children independently of age are negatively associated with oxidative damage to membrane lipids, whereas factors promoting goitrogenesis do not contribute to this process.

Evaluation of the effectiveness of iodine prophylaxis in Poland based on over 20 years of observations of iodine supply in school-aged children in the central region of the country

Introduction Due to the mild-to-moderate iodine deficiency in Poland, in 1997 iodine prophylaxis based on obligatory salt iodization was introduced. We attempted to evaluate the effectiveness of such prophylaxis, based on over 20 years of observations of iodine supply in school-aged children in Opoczno district (Central Poland). Material and methods A group of 603 children (316 girls and 287 boys), aged 6–14, was examined at 4 time points: in the years 1994, 1999, 2010 and 2016. The children were tested for urine iodine concentration (UIC) and in each child the thyroid volume was measured ultrasonographically. Results The median UIC in 1994 (45.5 μg/l) indicated moderate iodine deficiency, while after introducing prophylaxis it corresponded to adequate values (1999 – 101.1 μg/l, 2010 – 100.6 μg/l, 2016 – 288.3 μg/l); however, the last value was higher than the previous two. The thyroid size, assessed by ultrasonography and presented as volume/body surface area (V/BSA), in 1994 was 6.55 × 10–6 m; this value was higher than at other time points (2.73 × 10–6 m in 1999, 2.73 × 10–6 m in 2010, and 2.70 × 10–6 m in 2016). Conclusions Iodine prophylaxis has proved effective in eliminating iodine deficiency. In recent years, the diversification of iodine sources, despite the reduction of salt consumption, has led to an increase in median UIC to values close to the upper limit of UIC, accepted as normal. Further increase in iodine supply may be unfavourable for health; therefore constant monitoring of iodine prophylaxis is required.