Hypermethylation of a New Distal Sodium/Iodide Symporter (NIS) enhancer (NDE) is associated with reduced NIS expression in thyroid tumors.

CONTEXT: In thyroid tumors, reduced radioiodine uptake is associated with worse patient outcome concomitantly with low sodium/iodide symporter (NIS) mRNA expression. Previous studies showed that CpG-island methylation in the NIS proximal promoter does not correlate with mRNA expression. OBJECTIVES: The aim of the study was to identify new CpG-islands within the NIS 5'region and investigate the involvement of their methylation in NIS expression. DESIGN: DNA was obtained from 30 pairs of thyroid samples: tumor (T) and surrounding nontumor (NT) samples. All T samples had reduced NIS mRNA expression compared to NT samples. MAIN OUTCOME MEASURES: Methylation degree was quantified by bisulfite sequencing, and NIS expression by real-time PCR and Western blot. Reporter gene assays were performed to determine CpG-island functionality. Tumor cell cultures were treated with 5-Aza demethylating agent to determine NIS expression, methylation status, and (125)I uptake. RESULTS: We identified a new CpG-island2 with 14 CpG sites, located -2152/-1887 relative to ATG site. CpG-island2 was hypermethylated in T compared to NT samples, in both benign and malignant tumor groups. There was a significant inverse correlation between NIS mRNA expression and degree of CpG-island2 methylation in NT and T samples. This sequence increased the expression of a reporter gene; thus, it was considered a new enhancer. Cell culture treatments with 5-Aza reduced CpG-island2 methylation levels concomitantly with restoration of NIS mRNA and protein expression and (125)I uptake. CONCLUSIONS: We identified a new distal enhancer, NIS distal enhancer, that regulates gene expression through DNA methylation. This enhancer is hypermethylated in T compared to NT samples and is associated with decreased NIS expression in tumors. This epigenetic deregulation may be an early event in tumorigenesis.

BRAF: a tool in the decision to perform elective neck dissection?

BACKGROUND: Some studies have demonstrated a correlation between the presence of a BRAF mutation and aggressive characteristics, including lymph node metastasis in papillary thyroid carcinoma (PTC). Prophylactic central neck dissection (CND) has been proposed for treatment of PTC. Given the potential complications of CND, we undertook a prospective study to determine the correlation between the BRAF mutation and lymph node metastasis. METHODS: A total of 51 patients with PTC underwent total thyroidectomy and routine prophylactic CND. All patients were tested for the BRAF mutation. RESULTS: Positive lymph nodes were found in 54.9% of patients. The BRAF mutation was found in 15 patients (29%). BRAF was not correlated with lymph node metastases. Lymph node metastases were correlated with multifocality (p=0.005) and angiolymphatic invasion (p=0.003) in univariate analysis. Age was also significant in multivariate analysis. CONCLUSIONS: Testing for the BRAF mutation does not help in deciding whether or not to perform CND.

Expression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues.

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-beta/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-beta and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-beta and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-beta/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.

Expression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues / Expressão de proteínas SMAD, mediadores da sinalização de TGF-beta/activina, em tecidos de tiroide humana

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-β/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-β and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-β and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-β/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.

OBJETIVO: Investigar a expressão de proteínas SMAD em tecidos de tiroide humana desde que a inativação dos componentes da sinalização de TGF-β/activina é relatada em diversos tipos de câncer. SMAD 2 e SMAD3 fosforilados (pSMAD2/3) associados com SMAD4 induzem a transmissão do sinal gerado por TGF-β e activina, enquanto SMAD7 inibe essa sinalização intracelular. Embora TGF-β e activina exerçam efeitos antiproliferativos nas células foliculares da tiroide, tumores de tiroide expressam altos níveis dessas proteínas. MATERIAIS E MÉTODOS: A expressão proteica de SMADs foi avaliada em bócio multinodular, adenoma folicular, carcinomas papilífero e folicular por imuno-histoquímica. RESULTADOS: A expressão de pSMAD2/3, SMAD4 e SMAD7 foi observada tanto em tumores benignos como malignos da tiroide. Embora pSMAD2/3, SMAD4 e SMAD7 exibissem alta positividade citoplasmática em carcinomas, a positividade nuclear de pSMAD2/3 não foi diferente entre lesões benignas e malignas da tiroide. CONCLUSÕES: O achado da expressão de SMADs em células tiroidianas e a presença das proteínas pSMAD2/3 e SMAD4 no núcleo de células tumorais indicam propagação da sinalização TGF-β/activina. Contudo, a alta expressão de SMAD7 inibitório, principalmente em tumores malignos, poderia contribuir para atenuação da sinalização antiproliferativa de SMADs em carcinomas de tiroide.

Thyroid tissue analysis through Raman spectroscopy.

The diagnosis of thyroid pathologies is usually made by cytologic analysis of the fine needle aspiration (FNA) material. However, this procedure has a low sensitivity at times, presenting a variation of 2-37%. The application of optical spectroscopy in the characterization of alterations could result in the development of a minimally invasive and non-destructive method for the diagnosis of thyroid diseases. Thus, the objective of this work was to study the biochemical alterations of tissues and hormones (T3 and T4) of the thyroid gland by means of molecular vibrations probed by FT-Raman spectroscopy. Through the discriminative linear analysis of the Raman spectra of the tissue, it was possible to establish (in percentages) the correct classification index among the groups: goitre adjacent tissue, goitre nodular region, follicular adenoma, follicular carcinoma and papillary carcinoma. As a result of the comparison between the groups goitre adjacent tissue versus goitre nodular region, an index of 58.3% of correct classification was obtained; this percentage was considered low, and it was not possible to distinguish the Raman spectra of these groups. Between goitre (nodular region and adjacent tissue) versus papillary carcinoma, the index of correct classification was 64.9%, which was considered good. A relevant result was obtained in the analysis of the benign tissues (goitre and follicular adenoma) versus malignant tissues (papillary and follicular carcinomas), for which the index was 72.5% and considered good. It was also possible, by means of visual observation, to find similar vibrational modes in the hormones and pathologic tissues. In conclusion, some biochemical alterations, represented by the FT-Raman spectra, were identified that could possibly be used to classify histologic groups of the thyroid. However, more studies are necessary due to the difficulty in setting a standard for pathologic groups.

Anatomic landmarks for localization of the spinal accessory nerve.

This anatomical study examines the anatomic topography and landmarks for localization of the spinal accessory nerve (SAN) during surgical dissections in 40 fresh human cadavers (2 females and 38 males; ages from 22 to 89 years with a mean of 60 years). In the submandibular region, the SAN was found anteriorly to the transverse process of the atlas in 77.5% of the dissections. When the SAN crossed the posterior belly of the digastric muscle, the mean distance from the point of crossing to the tendon of the muscle was 1.75 +/- 0.54 cm. Distally, the SAN crossed between the two heads of the SCM muscle in 45% of the dissections and deep to the muscle in 55%. The SAN exited the posterior border of the sternocleidomastoid muscle in a point superior to the nerve point with a mean distance between these two anatomic parameters of 0.97 +/- 0.46 cm. The mean overall extracranial length of the SAN was 12.02 +/- 2.32 cm, whereas the mean length of the SAN in the posterior triangle was 5.27 +/- 1.52 cm. There were 2-10 lymph nodes in the SAN chain. In conclusion, the nerve point is one of the most reliable anatomic landmarks for localization of the SAN in surgical neck dissections. Although other anatomic parameters including the transverse process of the atlas and the digastric muscle can also be used to localize the SAN, the surgeon should be aware of the possibility of anatomic variations of those parameters. Similar to previous investigations, our results suggest that the number of lymph nodes of the SAN chain greatly varies.

Association of low sodium-iodide symporter messenger ribonucleic acid expression in malignant thyroid nodules with increased intracellular protein staining.

CONTEXT: The expression of sodium iodide symporter (NIS) is required for iodide uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide uptake. However, previous studies by RT-PCR or immunohistochemistry have shown divergent results of NIS expression in these nodules. OBJECTIVE: The objective of the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH receptor proteins expression, and localize the NIS protein in thyroid nodules samples and their surrounding nonnodular tissues (controls). DESIGN: NIS mRNA levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins, evaluated by immunohistochemistry, were examined in surgical specimens of 12 benign and 13 malignant nodules and control samples. RESULTS: When compared with controls, 83.3% of the benign and 100% of the malignant nodules had significantly lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant nodules had stronger intracellular NIS immunostaining than controls. Low gene expression associated with strong intracellular immunostaining was most frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS protein was located at the basolateral membrane in 24% of the control samples, 8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign nodules with strong TSH receptor positivity (41.6%) was higher than malignant (7.7%). CONCLUSION: We confirmed that reduced NIS mRNA expression in thyroid malignant nodules is associated with strong intracellular protein staining and may be related to the inability of the NIS protein to migrate to the cellular basolateral membrane. These results may explain the low iodide uptake of malignant nodules.

[Thyroid microcarcinoma: experience and management in private clinic]. / Microcarcinoma da tireóide: experiência e conduta em clínica privada.

OBJECTIVE: The study of papillary microcarcinoma observed during the thyroidectomies in our private clinic. MATERIAL AND METHODS: We reviewed clinical and histopathological results of 1,930 consecutive patients submitted for thyroidectomies in the period from 2002 to 2006, 606 had thyroid carcinomas but only 332 were papillary microcarcinoma. We studied gender, age, histologic type, size, multifocality, frequency of neck dissection, and results of Whole Body Scan and thyroglobulin. RESULTS: Overall, we found 48 males and 146 older than 45 years old. Therapy included total thyroidectomy for all, therapeutic neck dissection in 19 (5.72%), and radioiodine for 313 (94.27%). We found 5 patients with distant metastases (1.5%). After 1 year, from 170 submitted to WBS, we consider 141 free of disease, 21 have positive thyroglobulin antibody, 6 have thyroglobulin level above 2 ng/ml, being 1 with lung metastases and other with lymph node recurrence (0.3%). CONCLUSION: We recommend total thyroidectomy, therapeutic neck dissection and radioiodine ablation when present clinical and pathological risk factors.

Microcarcinoma da tireóide: experiência e conduta em clínica privada / Thyroid microcarcinoma: experience and management in private clinic

OBJETIVO: Estudar o microcarcinoma papilífero observado nas tireoidectomias realizadas em nossa clínica privada. MATERIAL E MÉTODOS: Revisamos clínica e histologicamente 1.930 pacientes submetidos a tireoidectomias no período de 2002 a 2006, tendo 606 carcinomas e, desses, 332 como microcarcinomas papilíferos. Avaliamos sexo, idade, tipo histológico, tamanho da neoplasia, multifocalidade, freqüência do esvaziamento cervical, resultados da PCI e tireoglobulina sérica. RESULTADOS: Dos 332 pacientes, 48 eram do sexo masculino e 146 tinham idade superior a 45 anos. Todos foram submetidos a tireoidectomia total, 19 concomitantemente a esvaziamento cervical de necessidade (5,72 por cento), e 313 a iodoterapia (94,27 por cento). Tivemos metástase a distância em 5 pacientes (1,5 por cento). Após 1 ano, de 170 pacientes submetidos à PCI, temos 141 considerados livres de doença, 21 com anti-tireoglobulina positivo, 6 com tireoglobulina superior a 2 ng/ml, sendo 1 com metástase pulmonar e outro com recidiva linfonodal (0,3 por cento). CONCLUSÃO: Recomendamos que seja realizada a tireoidectomia total, esvaziamento cervical de necessidade e iodoterapia ablativa na presença de fatores clínicos e anátomo-patológicos de risco.

OBJECTIVE: The study of papillary microcarcinoma observed during the thyroidectomies in our private clinic. MATERIAL AND METHODS: We reviewed clinical and histopathological results of 1,930 consecutive patients submitted for thyroidectomies in the period from 2002 to 2006, 606 had thyroid carcinomas but only 332 were papillary microcarcinoma. We studied gender, age, histologic type, size, multifocality, frequency of neck dissection, and results of Whole Body Scan and thyroglobulin. RESULTS: Overall, we found 48 males and 146 older than 45 years old. Therapy included total thyroidectomy for all, therapeutic neck dissection in 19 (5.72 percent), and radioiodine for 313 (94.27 percent). We found 5 patients with distant metastases (1.5 percent). After 1 year, from 170 submitted to WBS, we consider 141 free of disease, 21 have positive thyroglobulin antibody, 6 have thyroglobulin level above 2 ng/ml, being 1 with lung metastases and other with lymph node recurrence (0.3 percent). CONCLUSION: We recommend total thyroidectomy, therapeutic neck dissection and radioiodine ablation when present clinical and pathological risk factors.

O Polimorfismo no códon 98 do gene de galectina-3 não está associado a tumores benignos e malignos de tiróide / Polymorphism on codon 98 of the galectin-3 gene are not associated to benign and nalignant thyroid tumors / Polymorphism on codon 98 of the galectin-3 gene are not associated to benign and nalignant thyroid tumors

Galectina-3 é uma proteína multifuncional altamente expressa em câncer de tiróide. O gene de galectina-3 (LGALS3) apresenta vários candidatos a SNPs anotados, no entanto a relação entre estes SNPs e variações fenotípicas específicas relevantes à saúde não foi avaliada. Neste estudo, investigamos SNPs do LGALS3 e uma possível associação destes com a tumorigênese tiroidiana. A presença de SNPs do LGALS3 em linhagens de carcinoma de tiróide (WRO, NPA, TPC-1, ARO), tecidos tiroidianos de 55 pacientes com diagnóstico de bócio multinodular ou carcinoma papilífero e linfócitos do sangue periférico de 45 indivíduos saudáveis foi avaliada por seqüenciamento e SSCP. A análise da seqüência codificadora do LGALS3 mostrou que o sítio T98P apresenta uma grande variação genotípica, visto que observamos os padrões homozigoto (AA ou CC) e heterozigoto (AC). Em linhagens de carcinoma de tiróide, o genótipo da NPA no sítio T98P do LGALS3 é CC, enquanto TPC-1, WRO e ARO são AC. As freqüências genotípicas do T98P do LGALS3 observadas em bócio multinodular (AC= 67 por cento, AA= 23 por cento, CC= 10 por cento) e carcinoma papilífero (AC= 68 por cento, AA= 20 por cento, CC= 12 por cento) foram semelhante à freqüência observada na população controle (AC= 60 por cento, AA= 24 por cento, CC= 16 por cento). Em conclusão, não observamos associação entre o genótipo T98P do LGALS3 e o fenótipo de tumor benigno ou maligno de tiróide.

Galectin-3 is a multifunctional protein highly expressed in thyroid cancer. The galectin-3 gene (LGALS3) has several annotated candidates SNPs, however the relationship between galectin-3 SNPs and specific phenotypic variations relevant to health has not been evaluated. In this study, we investigated SNPs in the galectin-3 gene and a putative association with thyroid tumorigenesis. The presence of LGALS3 SNPs in thyroid carcinoma cell lines (NPA, TPC-1, WRO, ARO), thyroid tissues of 55 patients with multinodular goiter or papillary carcinoma diagnosis and lymphocytes of peripherical blood of 45 healthy individuals was evaluated by sequencing and SSCP. The analysis of LGALS3 coding sequence showed that the T98P site presents a great genotypic variation, since we observed both homozygous (AA or CC) and heterozygous (AC) patterns. In thyroid carcinoma cell lines, the genotype of NPA in the LGALS3 T98P site is CC, while TPC-1, WRO and ARO are AC. The genotypic frequency of T98P SNP observed in multinodular goiter (AC= 67 percent; AA= 23 percent; CC= 10 percent) and papillary carcinoma (AC= 68 percent; AA= 20 percent; CC= 12 percent) were similar to the frequency observed in the control population (AC= 60 percent, AA= 24 percent, CC= 16 percent). In conclusion, no association between LGALS3 T98P genotype and the phenotype of the benign or malignant thyroid tumor was observed.

[Polymorphism on codon 98 of the galectin-3 gene is not associated to benign and malignant thyroid tumors]. / O Polimorfismo no códon 98 do gene de galectina-3 não está associado a tumores benignos e malignos de tiróide.

Galectin-3 is a multifunctional protein highly expressed in thyroid cancer. The galectin-3 gene (LGALS3) has several annotated candidates SNPs, however the relationship between galectin-3 SNPs and specific phenotypic variations relevant to health has not been evaluated. In this study, we investigated SNPs in the galectin-3 gene and a putative association with thyroid tumorigenesis. The presence of LGALS3 SNPs in thyroid carcinoma cell lines (NPA, TPC-1, WRO, ARO), thyroid tissues of 55 patients with multinodular goiter or papillary carcinoma diagnosis and lymphocytes of peripheral blood of 45 healthy individuals was evaluated by sequencing and SSCP. The analysis of LGALS3 coding sequence showed that the T98P site presents a great genotypic variation, since we observed both homozygous (AA or CC) and heterozygous (AC) patterns. In thyroid carcinoma cell lines, the genotype of NPA in the LGALS3 T98P site is CC, while TPC-1, WRO and ARO are AC. The genotypic frequency of T98P SNP observed in multinodular goiter (AC= 67%; AA= 23%; CC= 10%) and papillary carcinoma (AC= 68%; AA= 20%; CC= 12%) were similar to the frequency observed in the control population (AC= 60%, AA= 24%, CC= 16%). In conclusion, no association between LGALS3 T98P genotype and the phenotype of the benign or malignant thyroid tumor was observed.

Total thyroidectomy for benign thyroid disease.

OBJECTIVES/HYPOTHESIS: The use of total thyroidectomy in thyroid cancer treatment is not unanimous, and it is even more controversial when this procedure is advocated for benign diseases. On the other hand, the complication risk may have an increase up to 20 times in repeat operations for recurrence. The objective of the study was to evaluate the use of total thyroidectomy in benign diseases, multinodular goiter, and Graves disease to justify the authors' preference. STUDY DESIGN: Retrospective study of use of total thyroidectomy in benign diseases. METHODS: Retrospective study of 1789 patients who underwent thyroidectomies from June 1990 to December 2000. Indication, extension of thyroidectomy, cancer incidence, and complications were analyzed. RESULTS: Total thyroidectomy was performed in 81.19% of 456 patients with nontoxic multinodular goiter, 93.93% of 33 with toxic multinodular goiter, 93.93% of 66 with recurrent multinodular goiter, and 49.18% of 122 with Graves disease. Thyroid cancer was found in 16.62%, 9.09%, 3.03% and 5.73% of patients, respectively. Transitory and permanent hypoparathyroidism, hematoma requiring surgical intervention, and transitory and permanent recurrent laryngeal nerve injury occurred in 12.27%, 1.61%, 0.26%, 1.88%, and 0.35% of the patients undergoing total thyroidectomy, respectively. Permanent complications of total thyroidectomy for nontoxic multinodular goiter and Graves disease were similar to nontotal thyroidectomy. Use of total thyroidectomy for nontoxic multinodular goiter increased from 53.33% of the patient to 81.19%, on average, with a concomitant increase of cancer diagnosis from 11.11% to 16,62%. The authors performed total thyroidectomy for all patients with Graves disease. CONCLUSION: Total thyroidectomy is the treatment of choice for multinodular goiter and thyroiditis, when there is bilateral gland involvement posterior to middle thyroid veins, and for Graves disease because it decreases the likelihood of future repeat operations for recurrent disease and thus the associated risks, when performed safely.

Tireoidectomia total para bócio multinodular / Total thyroidectomy for multinodular goiter

INTRODUÇÄO: Preservar tecido tireóideo em cirurgias para bócio multinodular (BM) näo evita a complementaçäo hormonal e pode gerar recidiva. A reoperaçäo aumenta em até 20 vezes o risco de complicações. Propomos no BM, a tireoidectomia total (TT) como tratamento definitivo quando existe acometimento bilateral do parênquima posterior à veia tireóidea média. OBJETIVO: Avaliar e justificar a utilizaçäo da TT em portadores de BM. MATERIAL E MÉTODO: Estudo retrospectivo de 1.789 pacientes submetidos a tireoidectomias de 06/90 a 12/00. A indicaçäo cirúrgica foi avaliada conforme a apresentaçäo clínica, a extensäo da tireoidectomia, a incidência de câncer e as complicações. RESULTADOS: A TT foi realizada em 81,2 por cento de 872 portadores de BM atóxicos, 93,9 por cento de 33 BM tóxicos e 93,9 por cento de 66 bócios recidivados. Houve hipoparatireoidismo transitório ou definitivo, hematoma e lesöes transitórias ou definitivas do nervo recorrente em respectivamente 11,5 por cento, 0,5 por cento, 0,4 por cento, 2,7 por cento e 0,2 por cento dos pacientes com BM atóxicos, e 8,3 por cento, 8,3 por cento, zero, 5,0 por cento e 5,0 por cento dos com B recidivados. Complicações definitivas da TT para BM atóxico foram semelhantes à tireoidectomia näo total, porém inferiores da TT para B recidivado. Ocorreu aumento da indicaçäo da TT para BM atóxico, com a utilizaçäo da veia tireóidea média como referência anatômica, de 53,3 por cento inicialmente para 93,6 por cento atualmente, com elevaçäo do diagnóstico de câncer de 11,1 por cento para 19,8 por cento. CONCLUSÄO: TT é o tratamento de escolha para o BM, quando acomete extensamente a glândula, isto é, posteriormente às veias tireóideas médias; com baixo índice de complicações definitivas

Activin betaB expression in rat experimental goiter and human thyroid tumors.

Activins are dimeric proteins of the transforming growth factor beta superfamily, which exhibit multiple functions in gonadal and extragonadal tissues. Expression of activin A, composed of two betaA subunits, has been shown in the thyroid, whereas there has been no study regarding activin B (betaBbetaB) in this gland. In other tissues, such as the gonads, pancreas, and adrenal cortex, expression of both activin betaA and activin betaB has been described. In this study, we detected activin betaB mRNA and protein expression using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in rat experimental goiter and in human thyroid, including multinodular goiter, follicular adenoma, papillary carcinoma, and follicular carcinoma. Activin betaA mRNA and protein expression was also investigated in rat and human thyroid tissue. The expression of both activin betaB and activin betaA was highest in rat methimazole-induced goiter and in human follicular adenoma, and papillary and follicular carcinomas when compared with multinodular goiter and normal thyroid tissue. The increased expression of activin betaB as well as activin betaA, observed in this study, suggests that activin B and activin A may be involved in the proliferative and neoplastic processes of the thyroid.

Galectin-3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors.

Galectin-3 is a protein of the lectin family that has been associated with neoplastic processes in various tissues. In the thyroid, expression of this protein has been described in differentiated follicular cancer, suggesting that the immunohistochemical study of galectin-3 may be a potential marker of malignancy in thyroid neoplasms. The confirmation of these results may represent an extremely useful tool for presurgical diagnosis and medical conduct. In this study, galectin-3 protein and mRNA expression were analyzed in the thyroid tissues from 87 patients with histomorphological diagnosis of multinodular goiter (MNG) (n = 24), follicular adenoma (n = 31), follicular carcinoma (n = 20), papillary carcinoma (n = 12), and five normal tissues. Galectin-3 protein expression was detected by immunohistochemical method in light, fluorescence, and confocal microscopy, using monoclonal antibody. Galectin-3 mRNA expression was detected by the RT-PCR method. Our results showed that the majority of carcinomas expressed galectin-3 protein (follicular, 90%; papillary, 100%). However, in contrast to the previously published data, benign lesions also expressed galectin-3 (adenoma, 45%; MNG, 17%). We further demonstrated by RT-PCR that thyroid tissues with diagnosis of adenoma and MNG-expressed galectin-3 mRNA. Although the galectin-3 immunostaining demonstrated a sensitivity of 93.8% in the identification of cancer, the accuracy in the distinction between benign and malignant tissues was 77.0%. This accuracy was even lower (68.6%) when the galectin-3 expression in follicular adenoma was compared with follicular carcinoma. Thus, the use of galectin-3 immunodetection as a molecular marker for thyroid carcinoma must be interpreted with caution, particularly in the differentiation between thyroid follicular carcinoma and follicular adenoma.