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PubMed1996

The aetiology, investigation and management of surgical disorders of the thyroid gland.

There have been many recent advances in our understanding of thyroid disease, including thyroid physiology, the molecular biology of thyroid neoplasms, guidelines for the management of surgical thyroid disease and the operative approach to thyroidectomy. The control of thyroid growth and function is better understood now that the thyroid stimulating hormone (TSH) receptor has been characterized as a G-protein coupled transmembrane receptor. The peripheral action of thyroid hormones is also better understood in terms of their interaction with nuclear thyroid hormone receptors. An adenoma-carcinoma sequence for the development of thyroid neoplasms has been proposed based on the characterization of a number of proto-oncogenes and tumour suppressor genes, and different pathways for the development of papillary and follicular thyroid carcinoma have been demonstrated. Fine needle biopsy has become, over the past few years, the principal diagnostic technique for evaluation of thyroid nodules, and has resulted in a significant reduction in the need for surgery for benign thyroid nodules. The approach to the management of thyroid carcinoma can now be based on comprehensive scoring systems for assigning patients to a particular risk group, the most recent of which is the MACIS system based on distant metastases (M), age (A), completeness of resection (C), invasion (I) and size (S). The capsular technique of thyroidectomy as described has now been shown to be the best method to preserve parathyroid blood supply, protect the recurrent laryngeal nerve and minimize the complications of thyroid surgery.

Drosophila Proteins↗
PubMed1991

DNA aneuploidy in follicular thyroid neoplasia.

The potential value of DNA aneuploidy, in distinguishing benign from malignant follicular thyroid neoplasms, was studied. The nuclear DNA content of 65 follicular thyroid neoplasms (52 adenomas and 13 carcinomas) was determined by flow cytometric analysis of paraffin embedded material; in 58 cases preparations were technically satisfactory. In 22 follicular neoplasms DNA analysis was also performed on fresh material obtained by fine needle aspiration of surgical specimens. Cell cycle analysis was performed on both fresh and fixed specimens. An aneuploid DNA profile was found on analysis of fixed tissue in eight of 45 (18 per cent) follicular adenomas and four of 13 (31 per cent) follicular carcinomas. DNA aneuploidy was also found in six of the 22 (27 per cent) fresh preparations from follicular adenomas. The frequency of DNA aneuploidy in apparently benign and malignant follicular neoplasms was similar. Follicular thyroid neoplasia are best regarded as a single entity with a low incidence of local and distant spread. All follicular neoplasia are therefore best excised.

Adenocarcinoma↗
PubMed2004

Gene expression profiling identifies platelet-derived growth factor as a diagnostic molecular marker for papillary thyroid carcinoma.

PURPOSE: Cancer diagnostics and therapeutics are often based on clinically relevant markers that are expressed specifically in a malignant tissue at levels higher than in normal tissue. We examined potential markers for papillary thyroid carcinoma (PTC) by monitoring PTC-specific gene expression using cDNA microarray. EXPERIMENTAL DESIGN: Gene expression profiles for PTC tissue, normal thyroid tissue, and healthy peripheral blood cells were compared by use of a human 4000-gene cDNA microarray. Protein expressions of the up-regulated genes in PTC were examined in thyroid tissues by immunohistochemistry. RESULTS: Sixty-four genes were overexpressed in PTC tissue relative to normal thyroid tissue and healthy peripheral blood cells. The genes that were up-regulated in PTC were involved in cell cycle regulation, DNA damage response, angiogenesis, and oncogenesis. Among these genes, basic fibroblast growth factor and platelet-derived growth factor were identified by immunochemical methods as proteins that are specifically expressed at high levels in thyroid neoplasms. Basic fibroblast growth factor, which has been identified as a biomarker for PTC, was overexpressed in 54% of PTC cases, 67% of follicular thyroid carcinomas, and 36% of benign thyroid neoplasms. Platelet-derived growth factor was overexpressed in 81% of PTC cases and 100% of follicular carcinomas, but was immunonegative in normal thyroid tissues and benign thyroid neoplasms. CONCLUSIONS: Platelet-derived growth factor may be a potential biomarker for PTC and follicular carcinoma. Expression profile analysis using a microarray followed by immunohistochemical study can be used to facilitate the development of molecular biomarkers for cancer.

Carcinoma, Papillary↗
PubMed1997

Galectin-3 and laminin expression in neoplastic and non-neoplastic thyroid tissue.

Galectin-3 is a 31 kD beta-galactoside-binding lectin which is expressed by several types of non-neoplastic and neoplastic cells and which may be involved in cell-extracellular matrix interactions. An immunohistochemical study has been made of the expression of galectin-3, as well as its ligand, laminin, in a spectrum of benign and malignant thyroid neoplasms and in some non-neoplastic conditions. Immunohistochemistry with anti-human recombinant galectin-3 antibody showed consistent, intense positivity in the neoplastic cells of 18 cases of papillary carcinoma and less intense staining in the five anaplastic carcinomas studied. In addition, two out of three poorly differentiated carcinomas, three out of six medullary carcinomas, and four out of eight follicular carcinomas had less intense or focal positivity. One case of Hürthle cell carcinoma showed scattered strongly positive cells. Eight follicular adenomas, three hyperplastic nodules, five nodular goitres, and normal thyroid tissue were negative. Galectin-3 mRNA expression was also evaluated in three of the papillary carcinomas, two follicular adenomas, and one hyperplastic nodule with matched normal tissue. Northern blot analysis demonstrated mRNA overexpression in the three cases of papillary carcinomas, whereas normal and benign tissues were negative. Laminin distribution in neoplastic and non-neoplastic tissue varied with architectural patterns but did not correlate with galectin-3 immunohistochemical expression. We conclude that expression of galectin-3 is limited to inflammatory foci in normal and benign thyroid tissue and is a phenotypic feature of malignant thyroid neoplasms, especially papillary carcinomas.

Antigens, Differentiation↗
PubMed1981

Serum lysozyme (muramidase) activity in dogs with neoplastic disease.

The lysozyme (muramidase) activity was measured in the sera of 84 dogs with neoplastic disease. Neoplasms included 32 lymphomas, 13 primary bone neoplasms, 5 melanomas, 5 thyroid neoplasms, 9 soft tissue sarcomas, 5 mast cell sarcomas, and 15 carcinomas. The sera from 21 healthy dogs served as control. Dogs with neoplastic disease had significantly (P less than 0.005) higher serum lysozyme activity than did the healthy controls. For lymphosarcoma, dogs with clinical signs of systemic disease had significantly higher serum lysozyme activity than did dogs without clinical signs. For bone neoplasms, dogs with metastatic disease had higher serum lysozyme activity than did dogs without metastasis. Increased lysozyme activity may be a useful marker of macrophage-mediated host responses to neoplasms in dogs.

Animals↗
PubMed1985

Epidermal growth factor receptors in normal and neoplastic thyroid tissue.

Epidermal growth factor (EGF) stimulates DNA synthesis and proliferation of thyroid cells in culture and may have an important role in the regulation of normal and neoplastic thyroid cell growth. We therefore studied paired normal and neoplastic thyroid tissue from eight patients for the presence of EGF receptors using a radioreceptor assay. 125I EGF binds to a particulate membrane fraction from both normal and neoplastic thyroid tissue with high affinity (dissociation constant ranged from 0.5 to 16.7 nmol/L). The binding is saturable, and maximal binding is achieved within 40 minutes at 37 degrees C and pH 7.5. This EGF binding is specific since it is competitively inhibited by unlabeled EGF but not by other hormones (thyrotropin, insulin, glucagon, and transferrin). The binding of EGF to thyroid neoplasms is higher than the binding to normal thyroid tissue (p less than 0.05). Thyroid tumors with a poorer prognosis appear to have higher EGF binding compared with adjacent normal thyroid tissue than have tumors with a better prognosis. EGF may have a role in the regulation of normal and neoplastic thyroid cell growth. Characterization of EGF receptors may help predict the clinical course of patients with malignant thyroid neoplasms.

Adenoma↗
PubMedDate not supplied

[Epidermoid carcinoma of the thyroid].

About thyroid neoplasms the epidermoidal carcinoma represents an ingrown minority (0.3-0.74%). Several etiopathological hypotheses are considered and this testifies the notable uncertainty that still winds the origin of the neoplasm. In the actual case, the more accredited hypothesis foresees the origin of the neoplasm from a histopathological of Hashimotos' tyhroiditis. The objectivity of the case in examination constitutes the clinical picture of reference of the malignant neoplasms of the thyroid: oligosintomatic low cervical mass of increased consistence, adherent to the imminent pianos strictly following laryngeal movements, dysfagia and dysfonia. Additionally they were present pulmonary and right cervical lymphonodal metastases. After an adjuvant treatment with Paraplatin and 5-FU, to some months from the intervention of total thyroidectomy, local relapse in form of a festered mass is highlighted in sovrajugular region with result in cutaneous-esophagustracheal fistula. The diagnosis of certainty of the neoplasm, despite the rarity, it doesn't constitute a problem, albeit the percents of survival, anyway substantially more favorable respect to anaplastic neoplasms, concerning to as numerical as chronological aspects, result to be hardly discouraging.

Aged↗
PubMed1976

[Thyroid malignant neoplasms. Therapeutic results in 305 patients].

Between 1960 and 1972, 305 patients with malignomas of the thyroid gland were surgically treated, irradiated (megavoltage therapy and/or iodine-131), and treated with thyroid hormone according to principles formerly stated. Differentiated adenocarcinomas (34.4% of all the patients) were observed more frequently in women and younger patients, whereas dedifferentiated carcinomas (33.8%) are found relatively more often in men and in an advanced age. Only in 12% of the cases the tumor was discovered in an early stage; thus, an early diagnosis is much too rare so far. In almost two thirds of the patients a spread of metastases occurred. Of these, 11% grew manifest later than five years following the therapy. Distant metastases from differentiated adenocarcinomas accumulated I-131 in sixty per cent, those from undifferentiated carcinomas still in twenty per cent. Treatment results are influenced decisively by histology, tumor spread, age and sex, women less than forty years old with differentiated adenocarcinomas and a circumscribed extension of the tumor having the best prognosis. More prognostic importance is due to the extension of the primary tumor than to the presence of metastases to regionary lymph nodes. Patients with metastases accumulating I-131 have a better chance of survival than those whose metastases do not accumulate. By means of standardized therapeutic rules, utilizing modern therapeutic techniques and based on interdepartmental cooperation, it was possible to improve the results partly by the two- or threefold as compared to a previously treated group of patients.

Adenocarcinoma↗
PubMed1984

Morphological classification and incidence of thyroid tumors in untreated aged mice.

The authors reviewed a total of 83 thyroid neoplasms in several strains of untreated mice. The 83 thyroid neoplasms consisted of 76 adenomas and 7 carcinomas. The adenomas and carcinomas were divided into the following three morphological types: papillary, follicular, and solid. The papillary adenoma was the most common type. The tumors were more common in female than male mice. The incidence ranged from 0.13% in BALB/c females to 8.6% in C3H-MTV females.

Adenoma↗
PubMed1996

Reexpression of thyroid peroxidase in a derivative of an undifferentiated thyroid carcinoma cell line by introduction of wild-type p53.

Loss of function of p53 is believed to result in transformation through impairment of its properties as a transcription factor, which interferes with the regulation of the cell cycle and under certain conditions, with programmed cell death. We report that stable transfection of clonal undifferentiated thyroid carcinoma cell lines harboring endogenous p53 mutations with a wild-type p53 expression vector only rarely yields transfectants expressing authentic wild-type p53. Among these, most exhibited an increase in doubling time and an impairment of colony formation in soft agar. Only one clonal wild-type p53-overexpressing derivative of the NPA papillary carcinoma cell line was obtained, and these cells were found to reexpress thyroid peroxidase (TPO). This clone also demonstrated reexpression of the paired box domain transcription factor Pax-8, which specifically activates transcription of TPO. Wild-type p53 did not directly stimulate transcriptional activity of a TPO promoter construct. Although the low frequency of authentic wild-type p53 stable transfectants limits the power of this analysis, these data suggest that in addition to its role in malignant transformation, p53 may be significant in the determination or maintenance of cell differentiation in thyroid neoplasms.

Base Sequence↗
PubMed1998

Thyroid metastasis from rectal carcinoma coexisting with Hashimoto's thyroiditis: gray-scale and power Doppler sonographic findings.

We present the gray-scale and power Doppler sonographic findings in a case of rectal carcinoma metastasis to the thyroid that mimicked a primary thyroid neoplasm and coexisted with Hashimoto's thyroiditis in a 67-year-old man. Gray-scale sonography revealed a hypoechoic mass with ill-defined borders in the left lobe of the thyroid; the mass extended through the isthmus to the right lobe. Sonography also showed multiple enlarged cervical lymph nodes. Power Doppler sonography showed increased flow in the nontumorous thyroid gland and decreased flow in the tumor. This contributed to the differentiation between the tumor and the remainder of the thyroid, which was involved with Hashimoto's thyroiditis.

Adenocarcinoma↗
PubMed1991

Increased stimulatory G protein in neoplastic human thyroid tissues.

Prior studies in our laboratory have shown that thyroid neoplasms produce increased amounts of cyclic adenosine monophosphate (cAMP). Thyroid-stimulating hormone receptors act through the stimulatory G protein (Gs) to activate adenylate cyclase, the enzyme responsible for cAMP production. The purpose of this study is to measure the activity and amount of Gs in human normal and neoplastic thyroid tissue to see whether alterations in Gs are responsible for the increased cAMP production seen in thyroid neoplasms. Four tumors with a high TSH-stimulated cyclase activity of 497.6 +/- 71.9 pmol/mg/30 min versus 35.9 +/- 13.5 pmol/mg/30 min for normal tissue from the same patients were studied. In reconstitution studies measuring Gs activity, neoplastic thyroid tissue produced 637 +/- 106 pmol cAMP/mg S49/mg thyroid membrane min versus 363 +/- 133 pmol cAMP/mg 549/mg thyroid membrane/min produced by normal thyroid tissue. Qualitative assessments of the amount of Gs present with cholera toxin-mediated adenosine diphosphate ribosylation showed increased Gs in thyroid tumors. Western blotting with antibodies directed against Gs showed a 3.3 +/- 0.6-fold increase in the amount of Gs in these thyroid tumors. These experiments identify an increase in the amount of an otherwise normal Gs as the biochemical defect responsible for the increased cAMP production in this group of tumors.

Adenocarcinoma↗
PubMed2001

Fine needle aspiration of the thyroid gland.

Fine needle aspiration (FNA) has become a major diagnostic triage for clinical management of patients with a thyroid mass. Diagnostic accuracy of this procedure can be evaluated by cyto-histologic correlation. Out of 1,761 fine needle aspirates of thyroid glands performed from January 1996 to December 1999, 230 satisfactory specimens contained respective histologic correlates. Using histologic diagnoses as the gold standard, the overall accuracy, sensitivity and specificity for cytologic diagnoses of thyroid neoplasm were 90.4 per cent, 85.7 per cent, and 92.5 per cent respectively. The positive predictive value for diagnosing thyroid neoplasm was 83.3 per cent while the negative predictive value was 93.7 per cent. The common pairs of cyto-histological diagnostic discrepancy included adenomatous goiter vs follicular neoplasm, adenomatous goiter vs papillary carcinoma, and thyroiditis vs follicular neoplasm. In conclusion, FNA is a rapid, reliable and safe diagnostic tool to distinguish non-neoplastic from neoplastic lesions in patients with thyroid masses.

Biopsy, Needle↗
PubMed2005

Cyclin D1 expression in primary thyroid carcinomas.

OBJECTIVES: The aim of the study was to demonstrate and evaluate the expression of cyclin D1, a protein connected with a cell cycle, by means of the immunohistochemical method in malignant thyroid neoplasms. The purpose of the analysis of the results was to explain the relation between cyclin D1 in thyroid cells and neoplasm transformation. MATERIAL AND METHODS: The study was conducted on thyroid neoplasms from 35 patients who were diagnosed with the thyroid carcinoma (30 women and 5 men). Detection DAKO LSAB + system was applied with use of monoclonal antibodies against cyclin D1. The results of immunohistochemical reaction was described as an index (percentage of cells showing a characteristic brown color in 1000 counted cells). As a positive result of reaction an intensive brown color of carcinomas cellular nuclei was acknowledged. RESULTS: The mean value of cyclin D1 expression index in papillary carcinoma was 14.44% +/- 9.37, in medullary carcinoma 27.35% +/- 5.40, in nonpapillary carcinomas originating from A cells 18.0% +/- 10.20. The results were statistically analyzed. In medullary carcinoma the highest values of positive cells cyclin D1 index were revealed. CONCLUSIONS: The results obtained encourage continued studies on cyclin D1 expression in thyroid neoplasms and a more accurate analysis with a larger number of cases. Perhaps the index of this protein will become a recognized prognostic marker in thyroid neoplasms or an objective risk factor of the thyroid epithelial cells neoplastic transformation.

Adolescent↗