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NCI CANCERLIT^® Search: Thyroid Cancer - June 2002

National Cancer Institute^®
Last Modified: June 1, 2002

Role of color flow Doppler sonography in pre-operative diagnostics of the thyroid pathology.
Thyroid carcinoma at King Edward VIII Hospital, Durban, South Africa.
Primary thyroid lymphoma: can the diagnosis be made solely by fine-needle aspiration?
Cost-effective management of thyroid nodules and nodular thyroid goiters.
Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a
Ganglioside reactive antibodies of IgG and IgM class in sera of patients with differentiated thyroid cancer.
Video-assisted thyroidectomy.
[Surgical tactics in benign nodal lesions of the thyroid]
[Radioactive iodine and thyroid tumors]
Differentiation between healthy thyroid remnants and tumor tissue after radioiodine therapy in patients with differentiated thyroid carcinoma
Nonpalpable thyroid nodules--managing an epidemic.
Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features.
Isozyme-specific abnormalities of PKC in thyroid cancer: evidence for post-transcriptional changes in PKC epsilon.
Mitogen-activated protein kinase cascade in human normal and tumoral parathyroid cells.
Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.
Pheochromocytoma multisystem crisis in a patient with multiple endocrine neoplasia type IIB and pyelonephritis.
Cyclin D1 overexpression in thyroid carcinomas: relation with clinico-pathological parameters, retinoblastoma gene product, and Ki67
Cyclin D1 in thyroid carcinomas.
Diagnosis of thyroid metastasis in cancer patients with thyroid mass by fine needle aspiration cytology and ultrasonography.
Use of recombinant thyrotropin.
Thyroid cancer 15 years after Chernobyl.
Thyroid cancer 15 years after Chernobyl.
Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten
The genetic background of medullary thyroid carcinoma in young patients.
p53, MDM2, bcl-2 staining in follicular neoplasms of the thyroid gland.
Expression of proteins: D1 cyclin and Ki-67 in papillary thyroid carcinomas.
Proliferative activity of the thyroid oxyphilic tumor cells estimated by means of quantitative analysis of silver stained nucleolar organizer
Molecular changes in thyroid neoplasia.
Genetic analysis of lithium-associated parathyroid tumors.
[Differentiated thyroid carcinoma. Surgery and significance of lymph node involvement.]
[Prophylactic total thyroidectomy in children and adolescents with genetic mutations in the RET-protooncogene.]
uPA receptor expression in benign and malignant thyroid tumors.
Occult thyroid carcinoma. A study of 160 autopsy cases. The first report for the region of Epirus-Greece.
Papillary thyroid cancer with pulmonary metastases in children: long-term prognosis.
Long-term outcome of children with papillary thyroid cancer.
[Reoperation of medullary thyroid carcinoma: long-term results]
MEN IIB and ganglioneuromatosis.
[Cancer of the thyroid gland]
Treatment of locally aggressive well-differentiated thyroid cancer.
[Thyroid cancer: epidemiology and predisposing mechanisms due to ionizing radiation]

1
UI - 11845109
AU - Giammanco M; Di Gesu G; Massenti MF; Di Trapani B; Vetri G
TI - Role of color flow Doppler sonography in pre-operative diagnostics of the thyroid pathology.
SO - Minerva Endocrinol 2002 Mar;27(1):1-10
AD - Department of Surgical, Anatomical and Oncological Science, University of Palermo, Italy. giammanco@interfree.it
BACKGROUND: The aim of this work is to demonstrate the high effectiveness of preoperative diagnosis by echotomographic study of thyroid nodules through color-Doppler sonography integrated by B-mode. The authors performed both B-mode ultrasonography and color-Doppler sonography on 125 patients expecting total thyroidectomy surgical intervention, without a previous evaluation of a number of other already performed clinical and instrumental tests. After the intervention, we compared the histologic test with the data drawn from the ultrasound scan, in order to demonstrate that color-Doppler sonography is able to provide for additional diagnostic information in the preoperative period. METHODS: One hundred and twenty five patients with thyroid pathologies were examined by both B-mode and color-Doppler sonography. Two diagnoses were made for each clinical case: the first supported by B-mode data, the second based on vascularity. Our aim was to check color-Doppler's ability to provide new information in the ultrasound diagnosis. All patients underwent a total thyroidectomy surgical intervention. The data were examined by K concordance test. RESULTS: Ultrasound data were compared with the histologic test, which showed 118 (97.4%) benign and 7 (5.6%) malignant lesions. B-mode ultrasound test gave a correct diagnosis in 115 (97%) out of 118 benign lesions and in 4 (57%) out of 7 malignant lesions, while 3 (2.5%) out of 118 cases were false positive and 3 (42.8%) out of 7 were false negative. In those cases showing a wrong conventional ultrasound diagnosis, after the integration of B-mode with color-Doppler results, a decrease was recorded in both false negative and false positive. CONCLUSIONS: Even if no correspondence was found between the different aspects of blood flow and the histologic types of lesions, this experience proves that the color-Doppler test has a high predictive value of benignity in cases with pattern I II and IV, while lesions with pattern III should be more carefully examined, since both malignant and benign lesions belong to this group. From the data drawn from this study, we are able to infer that color-Doppler sonography is undoubtedly an advantage not only in terms of cutting the false negatives, but also in the aim of obtaining a higher effectiveness in the screening of goitrogenic pathology.

2
UI - 12002083
AU - Mulaudzi TV; Ramdial PK; Madiba TE; Callaghan RA
TI - Thyroid carcinoma at King Edward VIII Hospital, Durban, South Africa.
SO - East Afr Med J 2001 May;78(5):242-5
AD - Department of Surgery, University of Natal and King Edward VIII Hospital, Durban, South Africa.
BACKGROUND: Western literature depicts papillary carcinoma as the most common thyroid malignancy followed by follicular carcinoma. OBJECTIVE: To assess the clinical pattern of thyroid carcinoma among African and Indian patients. SETTING: King Edward VIII Hospital, Durban, South Africa. DESIGN: A retrospective study. SUBJECTS: One hundred patients with thyroid carcinoma treated at a tertiary teaching hospital between 1990 and 1997. RESULTS: Seventy seven patients were Africans and 23 were Indians. The male to female ratio was 1:6. Ninety eight patients presented with goitre with or without regional lymph node involvement or distant disease. The duration of symptoms ranged from one to 360 months. The mean age at presentation was 48.6 +/- 16.0 years. Follicular carcinoma was the most common malignancy among African patients (68%), followed by papillary carcinoma (16%), anaplastic carcinoma (13%) and medullary carcinoma (2.6%). Papillary carcinoma was the most common malignancy among Indian patients (57%) followed by follicular carcinoma and medullary carcinoma. There was no anaplastic carcinoma among Indian patients. Fifty five patients underwent lobectomy with 32 undergoing subsequent completion thyroidectomy. Nine patients had near total thyroidectomy, 27 were offered total thyroidectomy as primary surgery and eight had biopsy only. The in-hospital mortality was 8%. Recurrence rate was 8%. CONCLUSION: Most patients present long after the development of symptoms. Follicular carcinoma is the most common thyroid malignancy among Africans. Further studies are required to explain this phenomenon.

3
UI - 11923138
AU - Cha C; Chen H; Westra WH; Udelsman R
TI - Primary thyroid lymphoma: can the diagnosis be made solely by fine-needle aspiration?
SO - Ann Surg Oncol 2002 Apr;9(3):298-302
AD - Department of Surgery, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA.
BACKGROUND: Primary malignant lymphoma of the thyroid accounts for <5% of all thyroid malignancies and is primarily treated with chemotherapy and external beam radiation. With the advent of modern immunophenotypic analyses, fine-needle aspiration (FNA) can potentially obviate the need for surgical procedures. METHODS: To investigate the utility of FNA, data from 23 consecutive patients with primary malignant thyroid 2000 were analyzed. RESULTS: Patients were categorized into two groups: those diagnosed before 1993 (group 1, n = 12) and those diagnosed after 1993 (group 2, n = 11). Although patients in group 1 were slightly older, there were no other differences between the groups with regard to sex, tumor grade, or tumor stage. Although no patient in group 1 was successfully diagnosed by FNA alone, seven patients (63%) in group 2 were diagnosed solely by FNA (P =.019, chi(2) analysis). Therefore, all 12 patients in group 1, but only 4 of 11 patients in group 2, required open surgical biopsy. CONCLUSIONS: Primary thyroid lymphoma is an uncommon malignancy usually treated nonsurgically once the diagnosis is established. In most patients with malignant lymphoma of the thyroid, FNA, should obviate the need for open surgical biopsy.

4
UI - 12005008
AU - Supit E; Peiris AN
TI - Cost-effective management of thyroid nodules and nodular thyroid goiters.
SO - South Med J 2002 May;95(5):514-9
AD - Mountain Home Veterans Affairs Medical Center, Johnson City, TN, USA.

5
UI - 12000737
AU - Maximo V; Soares P; Lima J; Cameselle-Teijeiro J; Sobrinho-Simoes M
TI - Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hurthle cell tumors.
SO - Am J Pathol 2002 May;160(5):1857-65
AD - Institute of Molecular Pathology and Immunology, the University of Porto, Porto, Portugal.
In an attempt to progress in the understanding of the relationship of mitochondrial DNA (mtDNA) alterations and thyroid tumorigenesis, we studied the mtDNA in 79 benign and malignant tumors (43 Hurthle and 36 non-Hurthle cell neoplasms) and respective normal parenchyma. The mtDNA common deletion (CD) was evaluated by semiquantitative polymerase chain reaction. Somatic point mutations and sequence variants of mtDNA were searched for in 66 tumors (59 patients) and adjacent parenchyma by direct sequencing of 70% of the mitochondrial genome (including all of the 13 OXPHOS system genes). We detected 57 somatic mutations, mostly transitions, in 34 tumors and 253 sequence variants in 59 patients. Follicular and papillary carcinomas carried a significantly higher prevalence of non-silent point mutations of complex I genes than adenomas. We also detected a significantly higher prevalence of complex I and complex IV sequence variants in the normal parenchyma adjacent to the malignant tumors. Every Hurthle cell tumor displayed a relatively high percentage (up to 16%) of mtDNA CD independently of the lesion's histotype. The percentage of deleted mtDNA molecules was significantly higher in tumors with D-loop mutations than in mtDNA stable tumors. Sequence variants of the ATPase 6 gene, one of the complex V genes thought to play a role in mtDNA maintenance and integrity in yeast, were significantly more prevalent in patients with Hurthle cell tumors than in patients with non-Hurthle cell neoplasms. We conclude that mtDNA variants and mtDNA somatic mutations of complex I and complex IV genes seem to be involved in thyroid tumorigenesis. Germline polymorphisms of the ATPase 6 gene are associated with the occurrence of mtDNA CD, the hallmark of Hurthle cell tumors.

6
UI - 11750045
AU - Lewartowska A; Pacuszka T; Adler G; Panasiewicz M; Wojciechowska W
TI - Ganglioside reactive antibodies of IgG and IgM class in sera of patients with differentiated thyroid cancer.
SO - Immunol Lett 2002 Feb 1;80(2):129-32
AD - Department of Clinical Biochemistry, Medical Centre of Postgraduate Education, Marymoncka 99, 01-813 Warsaw, Poland. alew@cmkp.edu.pl
We searched for the presence of ganglioside reactive antibodies in sera of patients with differentiated thyroid cancer (DTC). Sera were screened by ELISA with plates coated with GM3(NeuAc), GM3(NeuGc), GM2, GM1, FucGM1, GD3, GD1a or GD1b gangliosides. Ganglioside reactive antibodies were detected more frequently in sera of patients with DTC than in sera of healthy persons, in keeping with the possibility of autoimmunization during carcinogenesis. Antibodies of IgM and IgG classes reactive with FucGM1 occurred most often. However, the infrequent occurrence of ganglioside reactive antibodies, their low titer and lack of correlation between their presence and clinical condition of the patients indicate that determination of these antibodies has no diagnostic value in DTC.

7
UI - 12022601
AU - Bellantone R; Lombardi CP; Raffaelli M; Boscherini M; De Crea C; Traini
TI - E Video-assisted thyroidectomy.
SO - J Am Coll Surg 2002 May;194(5):610-4
AD - Department of Surgery, Universita Cattolica del Sacro Cuore, Rome, Italy.
BACKGROUND: In 1998, we developed a technique for video-assisted thyroidectomy (VAT). In this article we report on the entire series of patients who underwent VAT and discuss the results obtained. STUDY DESIGN: Forty-seven patients were selected for VAT. Eligibility criteria were: thyroid nodules of 35 mm or less in maximum diameter; estimated thyroid volume within normal range or slightly enlarged; small, low-risk papillary carcinomas; neither previous neck surgery nor irradiation; and no thyroiditis. After a learning period, VAT was proposed also for completion thyroidectomy (of previous video-assisted lobectomy) and nodules with maximum diameter up to 45 mm. The procedure is performed by a totally gasless video-assisted technique through a single 1.5- to 2.0-cm skin incision. Dissection is performed under endoscopic vision using a technique very similar to conventional operation. RESULTS: Fifty-three VATs were attempted on 47 patients. Thirty-three lobectomies, 10 total thyroidectomies, and 6 completion thyroidectomies were successfully performed. Six patients with papillary carcinoma underwent central neck lymph node removal by the same access. Mean operative time was 86.8 minutes for lobectomy, 116.0 minutes for total thyroidectomy, and 77.5 minutes for completion thyroidectomy. Conversion rate was 7.5%. Postoperative complications included one transient recurrent nerve palsy, three transient symptomatic postoperative hypocalcemias, and one wound infection. The cosmetic result was considered excellent by most of the patients who successfully underwent VAT. CONCLUSIONS: VAT is feasible and safe and allows for an excellent cosmetic result. Not all patients are eligible for this procedure, but in selected cases it can be a valid option for the surgical treatment of thyroid diseases.

8
UI - 11764578
AU - Kononenko SN
TI - [Surgical tactics in benign nodal lesions of the thyroid]
SO - Khirurgiia (Mosk) 2001;(11):24-7
Results of surgical treatment of 2307 patients with different forms of thyroid nodal diseases over 11 years (1989-2000) were analyzed. It is necessary to perform organ-saving operations to reduce postoperative complications rate and save hormone-producing function of the thyroid gland: after thyroid resection the rate of postoperative hypothyrosis was 7.9%, after hemithyreoidectomy and subtotal resection--92.4%. Recurrence was revealed in 10.7% cases in 3.7 years, on the average, that testifies to radical surgery. Resection with removal of node in limits of intact tissue was performed according to the results of morphologic examination of both node and surrounding thyroid tissue: discirculation with fibrosis were seen in 69.7%, dystrophic processes with secondary thyroiditis--in 24.3% cases. Etiology and morphology of the node are the main factors of pathogenesis of recurrence. Organ-saving operations and consideration of endocrinological aspects permitted to cure radically 89.3% patients.

9
UI - 11980328
AU - Fromigue J; Bachelot A; Baudin E; Schlumberger M
TI - [Radioactive iodine and thyroid tumors]
SO - Pathol Biol (Paris) 2002 Apr;50(3):157-60

10
UI - 12034413
AU - Moka D; Dietlein M; Raffelt K; Hahn J; Schicha H
TI - Differentiation between healthy thyroid remnants and tumor tissue after radioiodine therapy in patients with differentiated thyroid carcinoma using in vitro phosphorus-31 magnetic resonance spectroscopy.
SO - Am J Med 2002 Jun 1;112(8):634-41
AD - Department of Nuclear Medicine, University of Cologne, Koln, Germany.
BACKGROUND: The growth and spread of many tumors are triggered by changes in cell membrane metabolism, which can lead to systemic alterations in levels of phospholipids. We sought to determine whether plasma levels of several phospholipids could differentiate between healthy remnants of thyroid tissue and residual tumor tissue or metastases in patients with thyroid carcinoma. METHODS: We measured plasma phospholipid levels by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in blood samples from 30 patients with thyroid cancer who had been rendered hypothyroid in preparation for diagnostic or therapeutic administration of iodine-131. All patients had undergone total thyroidectomy. Iodine-131 whole-body scintigraphy and measurements of thyroglobulin values during up to 3 years of follow-up were used to distinguish patients in remission from those with only healthy thyroid remnants and those with tumor tissue or metastases. RESULTS: Mean (+/- SD) levels of sphingomyelin (0.33 +/- 0.06 mmol/L vs. 0.46 +/- 0.03 mmol/L, P <0.0001) and phosphatidylcholine (1.34 +/- 0.19 mmol/L vs. 2.15 +/- 0.33 mmol/L, P <0.0001) were significantly lower in patients with metastatic thyroid cancer (n = 8) than in patients (n = 12) who were in remission. Patients with only remnants of thyroid tissue (n = 10) also had significantly lower phospholipid levels than did patients in remission, but significantly greater levels that did patients with tumor tissue or metastases. CONCLUSION: These preliminary results suggest that 31P-MRS may be useful in helping to differentiate the presence of tumor tissue, remnants of thyroid tissue not requiring further treatment, and remission in patients with thyroid cancer.

11
UI - 11994320
AU - Ross DS
TI - Nonpalpable thyroid nodules--managing an epidemic.
SO - J Clin Endocrinol Metab 2002 May;87(5):1938-40

12
UI - 11994321
AU - Papini E; Guglielmi R; Bianchini A; Crescenzi A; Taccogna S; Nardi F;
TI - Panunzi C; Rinaldi R; Toscano V; Pacella CM Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features.
SO - J Clin Endocrinol Metab 2002 May;87(5):1941-6
AD - Department of Endocrine, Metabolic and Digestive Diseases, Ospedale Regina Apostolorum, Albano, Rome, Italy. papinie@virgilio.it
The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.

13
UI - 11994357
AU - Knauf JA; Ward LS; Nikiforov YE; Nikiforova M; Puxeddu E; Medvedovic M;
TI - Liron T; Mochly-Rosen D; Fagin JA Isozyme-specific abnormalities of PKC in thyroid cancer: evidence for post-transcriptional changes in PKC epsilon.
SO - J Clin Endocrinol Metab 2002 May;87(5):2150-9
AD - Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
PKC isozymes are the major binding proteins for tumor-promoting phorbol esters, and PKC activity is abnormal in a number of different human cancers. Less is known about putative structural and functional changes of specific PKC isozymes in human neoplasms. A single-point mutation of PKCalpha at position 881 of the coding sequence has been observed in human pituitary adenomas and up to 50% of thyroid follicular neoplasms, and a rearrangement of PKCepsilon was reported in a thyroid follicular carcinoma cell line, suggesting that these signaling proteins may play a role in thyroid tumorigenesis. To explore this possibility, we examined thyroid neoplasms for mutations and changes in expression levels of PKCepsilon or alpha. None of the 57 follicular adenomas, 26 papillary carcinomas (PCs), 7 follicular carcinomas, or the anaplastic carcinoma harbored the PKCalpha 881A>G mutation. Moreover, none of 15 PCs, 10 follicular adenomas, or 6 follicular carcinomas showed evidence of mutations of PKCepsilon. However, 8 of 11 PCs had major isozyme-specific reductions of the PKCepsilon protein, which occurred through either translational or posttranslational mechanisms. These data indicate that post-transcriptional changes in PKCepsilon are highly prevalent in thyroid tumors and may play a significant role in their development.

14
UI - 11994364
AU - Corbetta S; Lania A; Filopanti M; Vicentini L; Ballare E; Spada A
TI - Mitogen-activated protein kinase cascade in human normal and tumoral parathyroid cells.
SO - J Clin Endocrinol Metab 2002 May;87(5):2201-5
AD - Institute of Endocrine Science, Ospedale Maggiore IRCCS, Milan, Italy 20122.
The calcium-sensing receptor (CaR) activation has recently been shown to modulate the ERK1 and ERK2 cascade in different cell lines. The present study investigated this pathway in human normal and tumoral parathyroid cells. In cells from normal parathyroids and almost all hyperplasia increasing extracellular calcium concentrations (Ca(o)(2+)) induced a significant activation of ERK1 and -2, the percent stimulation over basal activity (at 0.5 mM Ca(o)(2+)) being 545 +/- 140 and 800 +/- 205 in normal cells and 290 +/- 71 and 350 +/- 73 in hyperplasia at 1 and 2 mM Ca(o)(2+), respectively. This effect was mediated by CaR because it was mimicked by the receptor agonist gadolinium and neomycin. Basal and Ca(o)(2+)-stimulated ERK1 and -2 activity was nearly abolished by the PKC inhibitor calphostin C, and PKA changes did not affect ERK1 and -2 activity. PI3K blockade by wortmannin, known to prevent G protein betagamma subunit effect on ERK1 and -2, induced a 30% reduction of the Ca(o)(2+)-stimulated ERK1 and -2 activity. Adenomatous cells showed high PKC-dependent ERK1 and -2 activity in resting conditions that was unresponsive to high Ca(o)(2+). A role of MAPK on PTH secretion was suggested by the finding that PD98059, a specific MEK inhibitor, abolished the inhibitory effect of 1.5 mM Ca(o)(2+) on PTH release from normal parathyroid cells. In conclusion, these data first demonstrate that CaR activation, through the PKC pathway and, to a lesser extent, PI3K, increases ERK1 and -2 activity in normal parathyroid cells and this cascade seems to be involved in the modulation of PTH secretion by Ca(o)(2+). Interestingly, this signaling pathway is disrupted in parathyroid tumors.

15
UI - 11994395
AU - Ringel MD; Hardy E; Bernet VJ; Burch HB; Schuppert F; Burman KD; Saji M
TI - Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.
SO - J Clin Endocrinol Metab 2002 May;87(5):2399
AD - Department of Medicine, Washington Hospital Center and MedStar Research Institute, Washington, D.C. 20010, USA. mathew.ringel@medstar.net
The development of distant metastasis is the most important predictor of death from thyroid cancer. KiSS-1 is a recently cloned human metastasis suppressor gene whose product, metastin, was recently identified as the endogenous agonist for a novel Gq/11 coupled receptor (metastin receptor). The expression and functional consequences of metastin and the metastin receptor have not been evaluated in thyroid cancer. We measured metastin and metastin receptor mRNA levels in 10 FCs and 13 papillary carcinomas (PCs), 2 benign non-functioning follicular adenomas (FAs), and 11 normal thyroid samples, and evaluated the signaling pathways activated by metastin in ARO thyroid cancer cells that express the metastin receptor endogenously. Paired normal and tumor samples were available for 4 PC and 3 PFC samples. Metastin mRNA was detected in 6/11 normal samples, and 0/2 FA, 2/10 FC, and 9/13 PC samples (p < 0.05 for PC vs. FC). Metastin receptor was not expressed in any normal thyroid or benign FA samples, and was expressed in only a minority (2/10) of FC samples. However, the receptor was expressed in the majority (10/13) of PCs (p = 0.002 for PC vs. normal tissue). Increased levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation of metastin receptor expressing ARO thyroid cancer cells with metastin resulted in activation of ERK, but not Akt. Taken together, these data suggest a potential role for metastin and/or metastin receptors in modulating the biological behavior of thyroid cancers.

16
UI - 12046054
AU - Caputo C; Fishbane S; Shapiro L; Courgi RG; Kostadinov S; Donovan V;
TI - Epstein D Pheochromocytoma multisystem crisis in a patient with multiple endocrine neoplasia type IIB and pyelonephritis.
SO - Am J Kidney Dis 2002 Jun;39(6):E23
AD - Division of Nephrology, and Department of Pathology, Winthrop-University Hospital, Mineola, NY, USA.
A patient with pyelonephritis developed multiorgan failure resulting in death. Clinical findings were consistent with multiple endocrine neoplasia type II, with bilateral pheochromocytomas identified by computed tomography scan. We hypothesize that either the infection or the administration of radiocontrast media led to a massive release of catecholamines from the pheochromocytomas. As a result, tissue perfusion was severely compromised, and multiorgan failure developed. This exceedingly rare complication of pheochromocytoma has been termed pheochromocytoma multisystem crisis. Copyright 2002 by the National Kidney Foundation, Inc.

17
UI - 11041450
AU - Basolo F; Caligo MA; Pinchera A; Fedeli F; Baldanzi A; Miccoli P;
TI - Iacconi P; Fontanini G; Pacini F Cyclin D1 overexpression in thyroid carcinomas: relation with clinico-pathological parameters, retinoblastoma gene product, and Ki67 labeling index.
SO - Thyroid 2000 Sep;10(9):741-6
AD - Department of Oncology, University of Pisa, Italy. f.basolo@do.mcd.unipi.it
Cyclin D1 is a G1 cyclin participating in the control of cell cycle progression through interaction with the retinoblastoma gene product (pRB). The overexpression of positive regulators (such as cyclin D1) has been reported in a variety of neoplasms, but their role in thyroid tumorigenesis is yet to be established. In our series of 54 thyroid carcinomas, cyclin D1 overexpression (detected by both immunohistochemistry and by Northern blotting) was correlated with prognostic variables, proliferative activity and pRB. Cyclin D1 overexpression was observed in 35% of thyroid carcinomas with a significantly higher expression of this cyclin in neoplastic tissues than in matched normal parenchyma. In well-differentiated carcinomas, the cyclin D1 mRNA overexpression was inversely correlated with nodal status (p = 0.03), while the protein product was higher in tumors from patients less than 40 than patients over 40 years of age. Inversely, there was no significant correlation with gender and tumor status, pRB and with proliferative activity.

18
UI - 11484902
AU - Shi Y; Zou M; Varkondi E; Nagy A; Kozma L; Farid NR
TI - Cyclin D1 in thyroid carcinomas.
SO - Thyroid 2001 Jul;11(7):709-10

19
UI - 12051452
AU - Li SY; Sheu WH; Chang MC; Tang KT; Lee TI; Lin HD
TI - Diagnosis of thyroid metastasis in cancer patients with thyroid mass by fine needle aspiration cytology and ultrasonography.
SO - Zhonghua Yi Xue Za Zhi (Taipei) 2002 Mar;65(3):101-5
AD - Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taiwan, ROC. sylin@vghtc.vghtc.gov.tw
BACKGROUND: Thyroid metastasis is generally thought to be infrequent. To evaluate its occurrence, fine needle aspiration cytology and ultrasound of the thyroid gland were performed in nonthyroid cancer patients with thyroid mass. METHODS: A total of 20 nonthyroid cancer patients (6 males and 14 females with a mean age of 55 +/- 7 years) with thyroid mass were examined with thyroid ultrasound and fine needle aspiration cytology. Their underlying malignancies included lung cancer in 10 patients, breast cancer in 7 patients, cervical cancer in 2 patients and colon cancer in 1 patient. RESULTS: Thyroid metastases were diagnosed in 4 patients (20%), 2 with breast cancer and 2 with lung cancer. For 3 of them, thyroid ultrasound showed solitary hypoechoic nodule, and in 1 case, multiple nodular lesions were demonstrated in each lobe. In addition, neck lymph nodes were noted in 3 patients. In the remaining 16 cancer patients, thyroid ultrasound showed either multiple or solitary nodular goiter change with no neck lymph node involvement. Fine needle aspiration cytology (FNAC) yielded nonthyroid adenocarcinoma in 4 metastatic cases. The 2 breast cancer patients received finally total thyroidectomy and were still alive 1 year after operation. While in the other 2 lung cancer cases, only supportive treatment were given due to advanced stages and the patients died within months. CONCLUSIONS: Thyroid metastases could occur at a high frequency in nonthyroid cancer patients with thyroid mass from our small series. By combining FNAC with ultrasound, a clinical diagnosis of thyroid metastasis is attainable in cancer patients with thyroid mass.

20
UI - 12057547
AU - Toft A; Beckett G
TI - Use of recombinant thyrotropin.
SO - Lancet 2002 Jun 1;359(9321):1874-5
AD - Endocrine Clinic and University Department of Clinical Biochemistry, Royal Infirmary, Edinburgh EH3 9YW, UK. Anthony.Toft@luht.scot.nhs.uk

21
UI - 12057579
AU - Zelicoff AP; Pezzullo JC
TI - Thyroid cancer 15 years after Chernobyl.
SO - Lancet 2002 Jun 1;359(9321):1946-7; discussion 1947

22
UI - 12057581
AU - Michel LA; Donckier JE
TI - Thyroid cancer 15 years after Chernobyl.
SO - Lancet 2002 Jun 1;359(9321):1947

23
UI - 11956824
AU - Ivanova R; Soares P; Castro P; Sobrinho-Simoes M
TI - Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten cases of an aggressive form of differentiated thyroid carcinoma.
SO - Virchows Arch 2002 Apr;440(4):418-24
AD - Laboratory of Pathomorphology, Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria.
In an attempt to advance and improve the characterization of the so-called diffuse follicular variant of papillary thyroid carcinoma (diffuse FVPTC) we studied a series of 59 thyroid carcinomas consecutively treated in a specialized center. The clinicopathologic and some of the immunohistochemical characteristics (uPA-R, Lewis X, Sialyl Lewis X, and MIB-1) of ten cases of FVPTC displaying a multinodular or diffuse pattern of growth, and histologic features similar to those previously described in diffuse FVPTC, were compared with those of common papillary thyroid carcinoma (PTC, 25 cases) and common FVPTC (8 cases). Cases of diffuse FVPTC differed significantly from common PTC and FVPTC in targeting younger patients and in exhibiting a prevalence of multicentricity, extrathyroid extension, nodal metastasis, and vascular invasion. Immunohistochemically, diffuse FVPTC cases were characterized by the overexpression of uPAR and sialyl Lewis X. No differences were observed regarding MIB 1 immunoreactivity. Regardless of the term used to designate the multicentric, invasive form of FVPTC (diffuse or multinodular FVPTC) it is crucial to acknowledge the existence of cases of FVPTC with a guarded prognosis that should be distinguished from the classic, uninodular form of FVPTC.

24
UI - 11820587
AU - Wiench M; Wygoda Z; Gubala E; Wloch J; Oczko M; Jarzab B
TI - The genetic background of medullary thyroid carcinoma in young patients.
SO - Folia Histochem Cytobiol 2001;39 Suppl 2():163-4
AD - Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Institute, Gliwice, Poland.
The study was undertaken to evaluate the frequency of RET polymorphisms at codons 769 and 836 in young medullary thyroid carcinoma (MTC) patients in whom the presence of a known germline mutation has been excluded. 40 patients aged 10-29 were subjected to genetic analysis of RET exons 10, 11, 13, 14 and 16 and compared to 140 older patients. The hereditary component occurred to be very high in young MTC patients: 57% carry the germline mutation, other 28% exhibit at least one rare polymorphic variant of RET. The observed allelic frequencies were 38% for polymorphic variant L769CTG and 6% for variant S836AGT. The results were significantly higher than those obtained in the group of older patients: 20% and 1% for L769CTG and S836AGT, respectively. Our results speak in favour that the polymorphism in RET codon 769 and 836 may also be a factor predisposing to the development of MTC in young age.

25
UI - 11820589
AU - Czyz W; Kuzdak K; Pasieka Z; Timler D; Brzezinski J
TI - p53, MDM2, bcl-2 staining in follicular neoplasms of the thyroid gland.
SO - Folia Histochem Cytobiol 2001;39 Suppl 2():167-8
AD - Dept of Endocrinological and General Surgery, Medical University, Lodz, Poland. chirendoclodz@poczta.onet.pl
Sixty-two follicular adenomas of the thyroid were investigated by immunohistochemistry for the expression of p53, MDM2 and bcl-2 proteins. The wild type of 393 aminoacid nuclear p53 phosphoprotein is the product of a gene located on the short arm of chromosome 17. The p53 protein controls the growth of transformed cells in a culture and thus termed a suppressor gene product. Mouse double minute 2 (MDM2) gene product has been described to occur in malignant epithelial tissue, the protein product of this gene binds to and presumably inactivates the growth suppressive effect of wild type p53 protein. Bcl-2 is an oncogene whose product inhibits apoptosis in many cells types. Some scattered nuclei in two adenomas (3.2%) stained positively for p53. The adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found, both patients are alive and well. In 12 adenomas (19%) there was positive reaction for MDM2 protein, whereas none of them where p53 positive. All cases were strongly positive for bcl-2 staining. We conclude that p53 protein expression is not confined to follicular adenomas, while MDM2 and bcl-2 genes products are.

26
UI - 11820608
AU - Timler D; Tazbir J; Matejkowska M; Gosek A; Czyz W; Brzezinski J
TI - Expression of proteins: D1 cyclin and Ki-67 in papillary thyroid carcinomas.
SO - Folia Histochem Cytobiol 2001;39 Suppl 2():201-2
AD - Department of Endocrinological and General Surgery, Medical University, Lodz, Poland. sokmr@poczta.onet.pl
The aim of the study was an evaluation of expression of D1 cyclin and Ki-67 proteins in tissue of human papillary thyroid carcinoma (PTC) in a group of papillary microcarcinomas and in a group of PTC with a degree of staging higher than pT1a in TNM classification. We performed immunohistochemical staining and found no statistical differences between groups. These results suggest that changes of expression of D1 cyclin are an early event in tumorigenesis.

27
UI - 11820609
AU - Augustynowicz A; Dzieciol J; Dadan J; Puchalski Z; Sulkowski S
TI - Proliferative activity of the thyroid oxyphilic tumor cells estimated by means of quantitative analysis of silver stained nucleolar organizer regions (AgNORs).
SO - Folia Histochem Cytobiol 2001;39 Suppl 2():203-4
AD - Department of Clinical Pathology, Medical Academy, Bialystok, Poland. albaug@poczta.onet.pl
Promising results of studies on different neoplasms, by means of morphometric analysis of argyrophilic nucleolar organizer regions (AgNORs), known as proliferative activity marker, made us undertake an attempt to evaluate of proliferative activity in Hurthle Cell Tumors using the same technique. 78 cases including 20 Hurthle Cell Carcinomas (HCC), 32 Hurthle Cell Adenomas (HCA) and 26 hyperplastic nodules with Hurthle Cell Metaplasia (HCM), diagnosed in the Department of Clinical Pathology, Medical Academy of Bialystok in the years 1990-2000, were subjected to analysis. For visualization of the NORs we used the D. Ploton et al. technique. Mean AgNOR count and NORDS (NOR distribution score--the percentage of nuclei with at least 5 argyrophilic granules) were estimated in each case in 100 randomly chosen nuclei. Non-parametric Mann-Whitney U-test was applied to determine statistically significant differences. RESULTS: Mean AgNoRs counts and NORDS values were 5.1 and 52%, 3.4 and 26%, 2.5 and 7% in HCC, HCA and HCM respectively. Statistically significant differences were found between AgNORs counts in carcinomas and adenomas (p<0.01), HCCs and HCMs (p<0.005) and betwveen NORDS in all groups (p<0.001).

28
UI - 11820615
AU - Jarzab B; Wloch J; Wiench M
TI - Molecular changes in thyroid neoplasia.
SO - Folia Histochem Cytobiol 2001;39 Suppl 2():26-7
AD - Dept of Nuclear Medicine and Endocrine Oncology, Clinic of Oncological Surgery, Maria Sklodowska-Curie Memorial Institute, Gliwice, Poland. bjarzab@io.gliwice.pl
All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.

30
UI - 11974460
AU - Gemsenjager E; Heitz PU; Martina B; Schweizer I
TI - [Differentiated thyroid carcinoma. Surgery and significance of lymph node involvement.]
SO - Chirurg 2002 Jan;73(1):38-43; discussion 43-5
AD - Chirurgische Klinik, Spital Zollikerberg (Neumunster), Zollikerberg/Zurich, Schweiz.
INTRODUCTION: Nodal treatment in papillary (PTC) and in follicular (FTC) thyroid carcinoma is still a subject of debate. METHODS: 1974-95 therapeutic lymphadenectomy (30/95), 1996-1999 frequent prophylactic lymphadenectomy (32/57; P = 0.005) was used for PTC, with therapeutic lymphadenectomy for FTC (15/115). 131I was used selectively for pN1-tumours. RESULTS: PTC: The incidence of pN0-, but not of pN1-status increased significantly (P = 0.03). Nodal recurrence was observed in 5/89 (6%) with therapeutic, vs. 1/54 (2%) with prophylactic lymphadenectomy (P = NS), i.e. in 1/107 (0.9%) patients without evidence of nodal disease, vs. 5/36 (14%) of those with pN1-status (P = 0.0004). Survival at 25 yrs. in stages TNM I and II was 100%, i.e., independent of N-status. FTC: No nodal recurrence was observed. CONCLUSION: Occult untreated nodal disease represented no major clinical problem. Selective nodal treatment may offer optimal results; meticulous nodal dissection is indicated for N1-tumours.

31
UI - 11938683
AU - Spinelli C; Puccini M; Bertocchini A; Lima M; Pacini F; Miccoli P
TI - [Prophylactic total thyroidectomy in children and adolescents with genetic mutations in the RET-protooncogene.]
SO - Pediatr Med Chir 2002 Jan-Feb;24(1):53-7
AD - Dipartimento di Chirurgica Generale, Universita di Pisa, Via Roma, 67, Pisa.
Medullary thyroid cancer (C.M.T.) can be a sporadic form generally in adults or a heredofamilial form where the first symptom appears in pediatric and adolescent age. The hereditary form can be isolated or associated with others endocrine neoplasias of type 2: MEN2a (with or without cutaneous lichen amyloidosis) and MEN2b. The responsible gene of the transmission has been identified in proto-oncogene RET localized on chromosome 10. Point form mutations of this proto-oncogene have been found on exons 10 and 11 in MEN2a and on 16 in MEN2b. In our study on 64 subjects, who belong 11 familiar groups, affected by MEN2a, MEN2b and familiar C.M.T., underwent a genetic research to look for point form mutations of proto-oncogene RET with PCR followed by the analysis of restriction. A genetic mutation has been revealed in 25 subjects: 18 were already known affected by MEN2 and so surgical treated and 7 seemed healthy (mean age 17.4 years, range 10-25). These 7 patients has been undergone clinical research and surgical treatment: a total thyroidectomy associated a lymphectomy of the central compartment. In all cases the histological exam showed C.M.T. moreover a patient had metastasis in lymph nodes of the central compartment. Another had hyperparathyroidism and pheochromocytoma treated with total thyroidectomy, parathyroidectomy and bilateral laparoscopic adrenalectomy. The identification in a very early age of carrier subjects of hill's gene inside an affected family, permits the execution of a prophylactic total thyroidectomy to prevent the C.M.T.. The penetrance of this neoplasia in hereditary form is 100%.

32
UI - 12017319
AU - Kim SJ; Shiba E; Taguchi T; Tsukamoto F; Miyoshi Y; Tanji Y; Takai S;
TI - Noguchi S uPA receptor expression in benign and malignant thyroid tumors.
SO - Anticancer Res 2002 Jan-Feb;22(1A):387-93
AD - Department of Surgical Oncology, Osaka University Medical School, Suita City, Japan. kimsj@onsurg.med.osaka-u.ac.jp
BACKGROUND: Urokinase type plasminogen activator receptor (uPAR) plays an important role in cancer invasion and metastasis. However, the uPAR expression has been rarely investigated in thyroid carcinomas. The aim of this study was to evaluate the clinical relevance of uPAR in thyroid tumors. MATERIALS AND METHODS: Samples included 53 benign tumors (follicular adenoma 34, Graves' disease 8, adenomatous goiter 7 and others 4) and 62 cancers (papillary thyroid cancer (PTC) 47, follicular TC (FTC) 5, medullary TC (MTC) 5 and anaplastic TC (ATC) 5). uPAR expression was prospectively investigated with a labeled streptavidin-biotin method using an anti-uPAR monoclonal antibody. Patients were classified into a low- and high-staining group according to the percentage of positive cells (cut-off value=10%). RESULTS: uPAR was more strongly expressed in thyroid cancers (35.5%) than benign tumors (7.5%). FTC had a significantly higher uPAR expression compared to follicular adenoma (p<0.01). The positivity of uPAR was as follows: PTC 36.2%, FTC 60%, MTC 0% and ATC 40%. In PTC, high uPAR expression was associated with poorly-differentiated PTC (p<0.01) while had a trend to develop more distant metastases than those with low uPAR expression (p=0.17, by the Kaplan-Meier method). CONCLUSION: This study has shown that uPAR expression might be useful for the discrimination between FTC and follicular adenoma and could possibly be used as a prognostic factor in PTC.

33
UI - 12017327
AU - Mitselou A; Vougiouklakis T; Peschos D; Dallas P; Agnantis NJ
TI - Occult thyroid carcinoma. A study of 160 autopsy cases. The first report for the region of Epirus-Greece.
SO - Anticancer Res 2002 Jan-Feb;22(1A):427-32
AD - Department of Forensic Pathology, Medical School, University of Ioannina, Greece.
Thyroid glands from 160 patients, aged 11 to 95 years, without known thyroid disease, collected from medicolegal autopsies, were sectioned at 3-5 mm slices and microscopically examined for occult disease. The glands were normal in 57.9%, while nodules were observed in 16.8% and adenomas in 10.6% of the cases. Carcinomas were found in 12 cases (7.7%) and occult papillary carcinomas in 5.6%. No carcinomas were found in the thyroids of patients less than 40 years of age. There were no significant differences in frequency of occult carcinomas between female and male patients. The diameter of these tumors was less than or equal to 5 mm, with one exception, which had a diameter more than 6 mm. The aim of this article is to provide data about the frequency of occult thyroid tumors in the population of Epirus, which is a district in the north west part of Greece.

34
UI - 11114619
AU - Brink JS; van Heerden JA; McIver B; Salomao DR; Farley DR; Grant CS;
TI - Thompson GB; Zimmerman D; Hay ID Papillary thyroid cancer with pulmonary metastases in children: long-term prognosis.
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