Cyclooxygenase-2 expression and its association with thyroid lesions

Cyclooxygenase (COX), also known as prostaglandin H synthase, catalyses the formation of prostaglandins from arachidonic acid. It can be expressed in response to various stimuli, such as hormones, mitogens, cytokines, other inflammatory mediators and growth factors. The product of COX-2 activity has been implicated in carcinogenesis by promoting angiogenesis, inhibiting apoptosis, increasing cell invasion and stimulating cell proliferation. It has also been proved that the regular intake of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the risk of developing colon and breast cancers. Thus, it speaks for an important role of COX-2 in growth processes of various types of neoplasms. The connection between COX-2 activity and carcinogenesis has also been examined in human thyroid neoplasms. COX-2 overexpression has been reported in thyroid cancers and also in inflammatory conditions. In consequence there is significant interest whether COX-2 could be of importance as a molecular marker of malignancy in the case of thyroid carcinoma

Relative quantification of PIK3CA gene expression level in fine-needle aspiration biopsy thyroid specimens collected from patients with papillary thyroid carcinoma and non-toxic goitre by real-time RT-PCR

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown that the phosphatidylinositol 3-kinase (PI3K) signaling pathway is important regulator of many cellular events, including apoptosis, proliferation and motility. PI3K pathway alterations (<it>PIK3CA </it>gene mutations and/or amplification) have been observed in various human tumours. In the majority of diagnosed cases, mutations are localized in one of the three "hot spots" in the gene, responsible for coding catalytic subunit α of class I PI3K (<it>PIK3CA</it>). Mutations and amplification of <it>PIK3CA </it>gene are characteristic for thyroid cancer, as well.</p> <p>Methods</p> <p>The aim of our study was to examine a gene expression level of <it>PIK3CA </it>in fine-needle aspiration biopsy (FNAB) thyroid specimens in two types of thyroid lesions, papillary thyroid carcinoma (PTC) and non-toxic goitre (NTG). Following conventional cytological examination, 42 thyroid FNAB specimens, received from patients with PTC (n = 20) and NTG (n = 22), were quantitatively evaluated regarding <it>PIK3CA </it>expression level by real-time PCR in the ABI PRISM^®7500 Sequence Detection System.</p> <p>Results</p> <p>Significantly higher expression level (RQ) of <it>PIK3CA </it>in PTC group has been noted in comparison with NTG group (p < 0.05).</p> <p>Conclusion</p> <p>These observations may suggest role of <it>PIK3CA </it>alterations in PTC carcinogenesis.</p

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

<p>Abstract</p> <p>Background</p> <p>COX-2 is an enzyme isoform that catalyses the formation of prostanoids from arachidonic acid. An increased <it>COX-2 </it>gene expression is believed to participate in carcinogenesis. Recent studies have shown that <it>COX-2 </it>up-regulation is associated with the development of numerous neoplasms, including skin, colorectal, breast, lung, stomach, pancreas and liver cancers. <it>COX-2 </it>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 <it>COX-2 </it>gene in mice. Despite the role of <it>COX-2 </it>expression remains a subject of numerous studies, its participation in carcinogenesis or the thyroid cancer progression remains unclear.</p> <p>Methods</p> <p>Twenty 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 <it>COX-2 </it>expression estimation. Total RNA was isolated (RNeasy Micro Kit), and RT reactions were performed. β-actin was used as endogenous control. Relative <it>COX-2 </it>expression was assessed in real-time PCR reactions by an ABI PRISM 7500 Sequence Detection System, using the ΔΔC_Tmethod.</p> <p>Results</p> <p><it>COX-2 </it>gene expression was higher in patients with PTC, when compared to specimens from patients with non-toxic nodular goitre (NTG).</p> <p>Conclusions</p> <p>The preliminary results may indicate <it>COX-2 </it>role in thyroid cancer pathogenesis, however the observed variability in results among particular subjects requires additional clinical data and tumor progression analysis.</p

Metastases of breast cancer to the thyroid gland in two patients - a case report

Introduction: Metastatic cancer is rarely found in the thyroid (only 2-3% of malignant tumours found in that gland); primary sources usually including breast, kidney, and lung tumours. Cases reports: Two cases of advanced breast cancer with thyroid metastases in female patients are presented. The similarities between these two cases included: 1) postmenopausal age; 2) diagnosis based on result of FNAB (numerous groups of cells with epithelial phenotype strongly implying metastatic breast cancer); 3) thyroid function - overt hyperthyroidism in the first woman and subclinical hyperthyroidism in the second one; 4) the presence of nodular goitre in clinical examination, the occurrence of many nodular solid normoechogenic lesions with calcifications in both thyroid lobes in US; and 5) negative antithyroid antibodies. The main difference was the time of establishing diagnosis; in the first woman - before mammectomy, parallel to diagnostics of breast tumour, and in the second woman four years after mammectomy, during cancer dissemination (with right pleural effusion and lung metastasis). In the first case, mammectomy was followed two weeks later by thyroidectomy. The second patient was disqualified from thyroid surgery due to systemic metastatic disease. Conclusions: 1. Fine needle aspiration biopsy of the thyroid gland should obligatorily be performed in patients with breast cancer and nodular goitre, even without any clinical data of metastatic disease. 2. The clinical context of cytological findings is of critical value. 3. In patients with breast cancer accompanied by multinodular goitre, we recommend that more punctures be performed during FNAB than is routinely done. (Pol J Endocrinol 2010; 61 (5): 512-515)Wstęp: Przerzuty do tarczycy są stosunkowo rzadko diagnozowane (2-3% złośliwych nowotworów tarczycy). Najczęściej narządem wyjściowym dla nowotworu przerzutowego są: sutek, nerka i płuco. Opis przypadków: Zaprezentowano przypadki 2 chorych z rozpoznanym rakiem sutka i przerzutami do tarczycy. Podobieństwa pomiędzy pacjentkami obejmują: 1) wiek pomenopauzalny; 2) ustalenie rozpoznania za pomocą BAC (liczne grupy komórek o fenotypie nabłonkowym, prawdopodobnie przerzut z raka sutka); 3) nadczynność tarczycy (jawna klinicznie u jednej pacjentki, subkliniczna u drugiej); 4) obecność wola guzkowego, w badaniu USG liczne lite zmiany ogniskowe normoechogeniczne, lite ze zwapnieniami w obu płatach tarczycy; 5) prawidłowe stężenia przeciwciał przeciwtarczycowych. Główną różnicą był moment postawienia rozpoznania; u pierwszej pacjentki przed mammektomią, równolegle do diagnostyki guza piersi, u drugiej 4 lata po mammektomii, w fazie rozsiewu choroby, z płynem w opłucnej i przerzutami do płuc. U pierwszej pacjentki przeprowadzono mammektomię, a dwa tygodnie później całkowitą tyreoidektomię, wdrożono substytucję L-tyroksyną i przekazano do dalszej terapii onkologicznej. Drugą pacjentkę zdyskwalifikowano z zabiegu z uwagi na stwierdzenie ogólnoustrojowego rozsiewu choroby. Wnioski: 1. Diagnostyka cytologiczna zmian ogniskowych w tarczycy u pacjentek z wywiadem raka sutka powinna być obligatoryjnie wykonywana, mimo braku jednoznacznych cech potwierdzających obecność zmian przerzutowych. 2. Kontekst kliniczny badania cytologicznego ma kluczowy charakter. 3. W przypadku podejrzenia przerzutu do tarczycy należy rozważyć możliwość poszerzenia zakresu badania cytologicznego w wolu wieloguzkowym poprzez selekcję większej liczby bioptowanych zmian ogniskowych. (Endokrynol Pol 2010; 61 (5): 512-515

Sudden onset of sarcoidosis after successful surgical treatment of Cushing’s syndrome

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Mechanisms of Normalisation of Bone Metabolism during Recovery from Hyperthyroidism: Potential Role for Sclerostin and Parathyroid Hormone

Sclerostin, a protein expressed by osteocytes, is a negative regulator of bone formation. The aim of the study was to investigate the relationship between parathyroid hormone (PTH) and markers of bone metabolism and changes of sclerostin concentrations before and after treatment of hyperthyroidism. Patients and Methods. The study involved 33 patients (26 women), age (mean ± SD) 48 ± 15 years, with hyperthyroidism. Serum sclerostin, PTH, calcium, and bone markers [osteocalcin (OC) and collagen type I cross-linked C-telopeptide I (CTX)] were measured at diagnosis of hyperthyroidism and after treatment with thiamazole. Results. After treatment of hyperthyroidism a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations was accompanied by marked decrease of serum sclerostin (from 43.7 ± 29.3 to 28.1 ± 18.4 pmol/L; p<0.001), OC (from 35.6 ± 22.0 to 27.0 ± 14.3 ng/mL; p<0.001), and CTX (from 0.49 ± 0.35 to 0.35 ± 0.23 ng/dL; p<0.005), accompanied by an increase of PTH (from 29.3 ± 14.9 to 39.8 ± 19.8; p<0.001). During hyperthyroidism there was a positive correlation between sclerostin and CTX (rs=0.41, p<0.05) and between OC and thyroid hormones (with FT3  rs=0.42, with FT4  rs=0.45, p<0.05). Conclusions. Successful treatment of hyperthyroidism results in a significant decrease in serum sclerostin and bone markers concentrations, accompanied by an increase of PTH

Successful treatment of thyrotoxicosis is accompanied by a decrease in serum sclerostin levels

Abstract Sclerostin, a product of a SOST gene, is a protein expressed by osteocytes that inhibits osteoblastic bone formation. Several hormones, including PTH and glucocorticosteroids, have been suggested to be possible regulators of sclerostin production. The influence of thyroid hormones on sclerostin synthesis has not been investigated, so far. The aim of the study was to evaluate sclerostin concentrations in patients before and after treatment of thyrotoxicosis. Patients and methods The study involved 15 patients (4 men), mean age 51.8±15.3 years, mean BMI value - 24.7±3.5, with thyrotoxicosis due to Graves’ disease or toxic multinodular goitre. Serum sclerostin was measured by immunoassay at diagnosis of thyrotoxicosis and after 6–10 weeks of treatment with thiamazole. The data were analysed by means of simple descriptive statistics of location and dispersion and Mann–Whitney U test for pairs of results, before and after thiamazole therapy. Association between variables was evaluated with use of Spearman`s correlation coefficient. Results There was a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations (from 8.74±4.79 pg/ml to 3.54±2.40 pg/ml, and from 4.48±2.21 ng/ml to 1.02±1.07 ng/ml, respectively, p3 or FT4 concentrations. Conclusions Restoration of a euthyroid state in patients with thyrotoxicosis results in a significant decrease in serum sclerostin concentrations. The above mentioned phenomenon may reflect lowering of bone metabolism, but a possible direct influence of thyroid hormones on SOST gene needs to be investigated.</p

Assessment of <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements in fine-needle aspiration biopsy specimens collected from patients with Hashimoto's thyroiditis

<p>Abstract</p> <p>Background</p> <p><it>RET/PTC </it>rearrangements are the most frequent molecular changes in papillary thyroid carcinoma (PTC). So far, 15 main <it>RET/PTC </it>rearrangements have been described, among which <it>RET/PTC1 </it>and <it>RET/PTC3 </it>are the most common in PTC - especially in radiation-induced tumours. <it>RET/PTC1 </it>and <it>RET/PTC3 </it>are the result of intrachromosomal paracentric inversions in chromosome 10, where <it>RET </it>and the activating genes (<it>H4 </it>and <it>ELE1</it>, respectively) are located. Recently, <it>RET/PTC </it>rearrangements have been shown not only in PTC but also in benign thyroid lesions, including Hashimoto's thyroiditis (HT). The aim of study was an assessment of <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements in patients with Hashimoto's thyroiditis.</p> <p>Materials and methods</p> <p>Thyroid aspirates, eligible for the study, were obtained from 26 patients with Hashimoto's thyroiditis by fine-needle aspiration biopsy (FNAB). Each aspirate was smeared for conventional cytology, while its remaining part was immediately washed out of the needle. The cells, obtained from the needle, were used in further investigation. Total RNA from FNAB was extracted by use of an RNeasy Micro Kit, based on modified Chomczynski and Sacchi's method and reverse transcription (RT-PCR) was done. Quantitative evaluation of <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements by real-time PCR was performed by an ABI PRISM^®7500 Sequence Detection System. In the study, PTC tissues with known <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements served as a reference standard (calibrator), while <it>β-actin </it>gene was used as endogenous control.</p> <p>Results</p> <p>Amplification reactions were done in triplicate for each examined sample. No <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements were found in the examined samples.</p> <p>Conclusions</p> <p>Our results indicate that <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements in Hashimoto's thyroiditis, if any, are rather rare events and further investigations should be conducted in order to determine molecular changes, connecting Hashimoto's thyroiditis with PTC.</p

The role of phosphoinositide 3-kinase subunits in chronic thyroiditis

<p>Abstract</p> <p>Background</p> <p>The 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 <it>PIK3CA</it>, <it>PIK3CB</it>, <it>PIK3CD</it> and <it>PIK3CG</it> genes expression levels in HT.</p> <p>Methods</p> <p>Following conventional cytological examination, 67 thyroid FNAB specimens, received from patients with HT, were quantitatively evaluated regarding <it>PIK3CA</it>, <it>PIK3CB</it>, <it>PIK3CD</it> and <it>PIK3CG</it> expression levels by real-time PCR in the ABI PRISM ^®7500 Sequence Detection System.</p> <p>Results</p> <p>The performed analysis has revealed significantly higher expression levels (RQ) of <it>PIK3CD</it>, <it>PIK3CG</it> and <it>PIK3CA</it> genes in comparison with <it>PIK3CB</it> gene (p<0.05) and significantly higher gene expression level of <it>PIK3CD</it> in comparison with <it>PIK3CA</it> (p<0.05).</p> <p>Conclusion</p> <p>The observed increased <it>PIK3CD</it>, <it>PIK3CG</it> genes expression in HT is probably related to lymphocyte infiltration commonly seen in this condition, however, the role of increased <it>PIK3CA</it> gene expression in the multi-step carcinogenesis process cannot be excluded.</p