Marco Aurélio Vamondes Kulcsar

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.

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.

MicroRNAs miR-146-5p and let-7f as prognostic tools for aggressive papillary thyroid carcinoma: a case report

Papillary thyroid cancer (PTC) is the most incident histotype of thyroid cancer. A certain fraction of PTC cases (5%) are irresponsive to conventional treatment, and refractory to radioiodine therapy. The current prognostic factors for aggressiveness are mainly based on tumor size, the presence of lymph node metastasis, extrathyroidal invasion and, more recently, the presence of the BRAFT1799A mutation. MicroRNAs (miRNAs) have been described as promising molecular markers for cancer as their deregulation is observed in a wide range of tumors. Recent studies indicate that the over-expression of miR-146b-5p is associated with aggressiveness and BRAFT1799A mutation. Furthermore, down-regulation of let-7f is observed in several types of tumors, including PTC. In this study, we evaluated the miR146b-5p and let-7f status in a young male patient with aggressive, BRAFT1799A-positive papillary thyroid carcinoma, with extensive lymph node metastases and short-time recurrence. The analysis of miR-146b-5p and let-7f expression revealed a distinct pattern from a cohort of PTC patients, suggesting caution in evaluating miRNA expression data as molecular markers of PTC diagnosis and prognosis.

Classification of papillary thyroid microcarcinoma according to size and fine-needle aspiration cytology: Behavior and therapeutic implications

The purpose of this study was to assess and classify cases of papillary microcarcinoma according to size (up to 0.5 cm and between 0.6 and 1.0 cm) and fine‐needle aspiration cytology (FNAC). These results were then correlated with clinical and histopathologic factors of worse prognosis.

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

INTRODUCTION Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. OBJECTIVE The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. MATERIALS AND METHODS After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. RESULTS Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. CONCLUSIONS MTC should be suspected in individuals who present with thyroid nodules and family histories of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation. Surgery represents the only curative therapeutic strategy. The therapeutic options for metastatic disease remain limited and are restricted to disease control. Judicious postoperative assessments that focus on the identification of residual or recurrent disease are of paramount importance when defining the follow-up and later therapeutic management strategies.

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. Clin. Anat. 22:471–475, 2009.

Activin βB 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.

Efficacy of pectoralis major muscle flap for pharyngocutaneous fistula prevention in salvage total laryngectomy: A systematic review.

The role of pectoralis major muscle flap (PMMF) in reducing the rate of pharyngocutaneous fistula after salvage total laryngectomy has not been clearly established. The purpose of this study was to evaluate the impact of PMMF in reducing pharyngocutaneous fistula rates after total laryngectomy.

External validation of the AJCC Cancer Staging Manual, 8th edition, in an independent cohort of oral cancer patients

OBJECTIVES To evaluate the new American Joint Committee on Cancer (AJCC) cancer staging manual (8th edition) in an independent cohort of patients surgically treated for oral squamous cell carcinoma in order to determine whether the upstaging of pT and pN classification was indicative of a worse prognosis. METHODS A cohort of 298 patients was analyzed retrospectively. RESULTS Of these patients, 22.8% received an upstaging when the depth of invasion was included into the pT classification. Similarly, 29.2% of them were upstaged when extracapsular extension was added to pN classification. Twenty-eight of 68 patients (41.2%) that received an upstaging of pT classification died, and 23 (33.8%) experienced disease recurrence compared to 98/229 (42.8%) and 68/229 (29.7%), respectively, for those with the same pT during follow-up. With regard to pN classification, 70.6% of upstaged patients (60/85) died, and 50.6% (43/85) developed recurrence of the disease compared to 63/205 (30.7%) and 42/205 (20.5%), respectively, for those with the same pN during follow-up. Patients who were upstaged in pT classification presented a worse DFS (51.1% versus 80.4%, P=0.007) and OS (31.5% versus 58.6%, P=0.017). Similarly, those that were upstaged in pN classification presented a worse DFS (17.1% versus 61.2%, P=0.001) and OS (8.5% versus 37.9%, P<0.001). CONCLUSION The new AJCC cancer staging manual (8th edition) allows a better stratification of oral SCC patients. By including the depth of invasion to the pT classification and extranodal extension to the pN classification, a worse disease-free and overall survival was assessed for these patients.

Oral cavity squamous cell carcinoma: factors related to occult lymph node metastasis.

INTRODUCTION Elective neck dissection is recommended in cases of oral cavity squamous cell carcinoma without lymph node metastasis because of the risk of occult metastasis. OBJECTIVE The present study aimed to evaluate predictive factors for occult lymph node metastasis in patients with oral cavity squamous cell carcinoma treated with elective neck dissection and their impact on overall and disease-free survival. METHODS Forty surgically treated patients were retrospectively included. RESULTS Ten cases (25%) had lymphatic metastasis. Of the studied variables, perineural and angiolymphatic invasion in addition to tumor thickness were statistically associated with lymph node metastasis. Only angiolymphatic invasion was identified as an independent risk factor for occult metastasis in the logistic regression (OR=39.3; p=0.002). There was no association between overall and disease-free survival with the presence of occult lymph node metastasis. CONCLUSION Metastatic disease rate was similar to that found in the literature. Perineural and angiolymphatic invasion and tumor thickness were associated with occult metastasis, but only angiolymphatic invasion showed to be an independent risk factor.Introduction Elective neck dissection is recommended in cases of oral cavity squamous cell carcinoma without lymph node metastasis because of the risk of occult metastasis.