RESUMEN
BACKGROUND/OBJECTIVE: The diagnostic accuracy of fine needle aspiration biopsy (FNAB) seems limited in large thyroid nodules with Bethesda Cat. 2 result. We aimed to determine the incidence of carcinoma with benign cytology and the reason for the high false-positive rate in thyroid nodules ≥4 cm. METHODS: The records of 103 patients with thyroid nodules ≥4 cm with preoperative cytological diagnosis of Bethesda Cat. 2 who underwent thyroidectomy were consecutively reviewed. Characteristics between patients with malignant vs. benign pathology were compared. RESULTS: Forty patients (38.8%) had malignancy. Malignancy was subclassified into follicular variant of papillary thyroid carcinoma (43%), minimally invasive follicular thyroid carcinoma (20.0%), and minimally invasive Hurthle cell thyroid carcinoma (10.9%). Patients with malignant cytology had significantly more suspicious ultrasound findings than those with benign cytology (p = 0.001). CONCLUSIONS: Preoperative FNAB showed high false-negative rates in patients with thyroid nodules ≥4 cm with benign cytology. These nodules have a high malignancy rate with suspicious ultrasound findings.
Asunto(s)
Adenocarcinoma Folicular , Neoplasias de la Tiroides , Nódulo Tiroideo , Adenocarcinoma Folicular/patología , Biopsia con Aguja Fina , Humanos , Estudios Retrospectivos , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/cirugía , TiroidectomíaRESUMEN
The incidence rates of structural persistent disease (PD) and recurrent disease (RD) after thyroidectomy, and their clinicoradiological (CT) characteristics, remain poorly understood. Therefore, we characterized differentiated thyroid cancer (DTC) patients who underwent re-operations, with a focus on preoperative CT scans. We examined neck CT scans obtained prior to initial surgery and reoperation, and classified the disease into four categories according to the persistence/recurrence and neck dissection/non-dissection status. In total, 121 of 9,173 DTC patients underwent reoperations to treat PD or RD; the mean time to reoperation was 25.5 and 54.1 months, respectively. Of all reoperations, 19% (23/121) were performed to treat RD; 81% (98/121) were performed to treat PD. Compared to RD, PD was commonly detected in the non-dissected neck. Tumor multiplicity and the number of pathologically positive lymph nodes were greater in the non-dissected than dissected neck. A review of the CT data revealed more false-negative findings on the 60-s- versus 30-40-s-delay scans of PD patients with non-dissected necks. In conclusion, most of the reoperations performed on DTC patients were for management of PD. Improved preoperative CT assessments and initial surgery, based on the information of clinico-radiological characteristics, are required in the care of DTC patients.
Asunto(s)
Recurrencia Local de Neoplasia , Cuidados Preoperatorios , Reoperación , Neoplasias de la Tiroides , Tiroidectomía , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Reacciones Falso Negativas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugíaRESUMEN
PURPOSE: An intermediate cervical plexus block (CPB) targets the posterior cervical space between the sternocleidomastoid muscle and the prevertebral fascia. The phrenic nerve descends obliquely on the surface of the anterior scalene muscle beneath the prevertebral fascia after originating from the C3-C5 ventral rami. Therefore, the phrenic nerve can be affected by a local anesthetic during an intermediate CPB, depending on the permeability characteristics of the prevertebral fascia. This study investigated whether an intermediate CPB affects the phrenic nerve, inducing hemidiaphragmatic paresis. METHODS: In this prospective observational study, 20 patients undergoing single-incision transaxillary robot-assisted right thyroidectomy were enrolled. The intermediate CPB (0.25% ropivacaine 0.2 ml/kg) was performed at the C4-5 intervertebral level carefully, without penetrating the prevertebral fascia, before the patient emerged from general anesthesia. Diaphragmatic motions of the block side were measured by M-mode ultrasonography at three time points: before anesthesia (baseline) and at 30 and 60 min after the intermediate CPB. Hemidiaphragmatic paresis was divided into three grades, depending on the percentage of diaphragm movement compared to the baseline: none (> 75%), partial paresis (25-75%), and complete paresis (< 25%). RESULTS: No patient showed any partial or complete ipsilateral hemidiaphragmatic paresis within 60 min after the intermediate CPB. CONCLUSION: Intermediate CPB using 0.2 ml/kg of 0.25% ropivacaine at the C4-5 intervertebral level did not cause ipsilateral hemidiaphragmatic paresis. This may imply that the effect of the intermediate CPB on the phrenic nerve is not significant.
Asunto(s)
Bloqueo del Plexo Cervical , Parálisis Respiratoria , Anestésicos Locales/efectos adversos , Plexo Cervical , Bloqueo del Plexo Cervical/efectos adversos , Humanos , Incidencia , Paresia/epidemiología , Paresia/etiología , Parálisis Respiratoria/diagnóstico por imagen , Parálisis Respiratoria/epidemiología , Parálisis Respiratoria/etiología , Ultrasonografía , Ultrasonografía IntervencionalRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
BACKGROUND: Whether chronic lymphocytic thyroiditis (CLT) influences the risk of development and the progression of papillary thyroid cancer (PTC) remains uncertain. We investigated the effects of CLT on the clinicopathologic features and prognosis of PTC. METHODS: Two thousand nine hundred twenty-eight consecutive patients with PTC treated between 2009 and 2017 were divided into two groups: one with chronic lymphocytic thyroiditis and one without; 1174 (40%) of the patients had coincident CLT. RESULTS: In univariate analysis, CLT correlated positively with small tumor size, frequent extrathyroidal extension, multifocal diseases, and p53 but negatively with central lymph node (LN) metastasis and BRAF mutation. In multivariate analysis, CLT was associated with extrathyroidal extension and multifocal disease; however, it was not a prognostic factor for recurrence even though it was associated with two aggressive factors. Compared with patients with PTC alone, there were more retrieved central LNs in the PTC + CLT group, and these patients also underwent more invasive diagnostic tests such as fine needle aspiration cytology and frozen biopsy of LN. CONCLUSIONS: The CLT patients with PTC had better behavior features and prognoses than did those with PTC alone despite frequent multifocality and extrathyroidal extension. However, precaution may be necessary to avoid performing invasive diagnostic procedures for lateral LN metastasis and to manage the patients appropriately.
Asunto(s)
Enfermedad de Hashimoto/patología , Recurrencia Local de Neoplasia/patología , Lesiones Precancerosas/patología , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adulto , Anciano , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Enfermedad de Hashimoto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Lesiones Precancerosas/inmunología , Pronóstico , Estudios Retrospectivos , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/inmunología , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
This study investigated the correlation between basal thyroglobulin (Tg) and recombinant human thyroid-stimulating hormone (rhTSH)-stimulated Tg in differentiated patients with thyroid cancer, and sought to determine whether the basal Tg level predicts the rhTSH-stimulated Tg level.We retrospectively enrolled 177 patients with papillary thyroid cancer (mean age =â44 years; 50 males, 127 females) who received rhTSH before radioiodine therapy (RIT). Serum Tg levels were measured 7 days before the 1st rhTSH injection (basal Tg) and on the days of RIT (rhTSH-stimulated Tg). Patients were divided into 3 groups according to rhTSH-stimulated Tg cut-off levels of 2, 5, and 10âng/mL. The correlation between basal Tg and rhTSH-stimulated Tg levels was assessed, and whether basal Tg was useful in predicting the rhTSH-stimulated Tg level was determined.A significant positive correlation was observed between basal and rhTSH-stimulated Tg levels (|rho| =â0.48, Pâ<â.0001). The basal Tg level had significant diagnostic ability in predicting an rhTSH-stimulated Tg level of 2âng/mL or higher, and the optimal basal Tg level for this prediction was 0.3âng/mL (AUC =â0.77, Pâ<â.0001). A basal Tg level of 0.5âng/mL was optimal for predicting rhTSH-stimulated Tg levels of 5âng/mL or higher (AUC =â0.81, Pâ<â.0001), and of 10âng/mL or higher (AUC =â0.82, Pâ=â.0171).The basal Tg level was significantly correlated with the rhTSH-stimulated Tg level. If the basal Tg level is >0.3 or 0.5âng/mL, then the rhTSH-stimulated Tg level can be expected to be sufficiently high to necessitate clinical examination.
Asunto(s)
Tiroglobulina/sangre , Cáncer Papilar Tiroideo/sangre , Neoplasias de la Tiroides/sangre , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , TirotropinaRESUMEN
PURPOSE: We investigated the risk factors of indeterminate response (IDR) in patients who underwent recombinant human thyroid-stimulating hormone (rhTSH)-aided radioactive iodine therapy (RAIT). METHODS: A total of 128 patients with papillary thyroid cancer were included in this retrospective study. The patients were classified into excellent response and IDR groups based on follow-up diagnostic whole-body scintigraphy (WBS) and TSH-stimulated thyroglobulin (Tg). Indeterminate response was defined as the presence of a faint uptake in the thyroid bed on the diagnostic WBS or a TSH-stimulated Tg detectable, but less than 10 ng/mL. Parameters that act as significant risk factors for IDR, including age, sex, stage, surgeon, time interval between surgery and RAIT, post-treatment WBS finding, urine iodine-to-creatinine ratio, TSH-unstimulated Tg, and rhTSH-stimulated Tg, were analyzed using a Cox proportional hazards regression method. RESULTS: After treatment, 64 patients showed IDR. Recombinant human TSH-stimulated Tg was the only independent risk factor for predicting IDR. Patients with an rhTSH-stimulated Tg greater than 2 ng/mL prior to RAIT were 3.75 times more likely (95% confidence interval, 1.61-8.72) to have an IDR than those with a lower rhTSH-stimulated Tg (≤2 ng/mL). CONCLUSIONS: Pre-RAIT TSH-stimulated Tg levels are a risk factor for IDR after RAIT.
Asunto(s)
Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Adulto , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/tratamiento farmacológico , Tirotropina/uso terapéutico , Resultado del Tratamiento , Imagen de Cuerpo EnteroRESUMEN
Calcification is important for the diagnosis of papillary thyroid carcinoma (PTC). Runt-related transcription factor 2 (RUNX2), a master transcription factor associated with osteogenic differentiation, is reportedly related to PTC calcification and invasiveness. However, its regulatory role in this process is somewhat uncharacterized. Here, we attempted to identify genes that regulate RUNX2 and clarify its function in PTC carcinogenesis and calcification. The expression of RUNX2-upstream genes was evaluated by real-time PCR in Nthy-Ori 3-1 normal thyroid cells and TPC1 and BHP10-3 PTC cell lines. Luciferase and chromatin immunoprecipitation assays were performed with candidate genes after cloning the RUNX2 promoter. We found that RUNX2 promoter activity was enhanced by homeobox family A9 (HOXA9). Over-expression of HOXA9 was found to enhance alkaline phosphatase activity, mineralization, and in vitro tumour cell migration and invasion, whereas downregulation had the opposite effects. These results indicate that HOXA9, a positive regulator of RUNX2, can enhance calcification, migration, and invasion in PTC. Our data improve the understanding of the molecular mechanisms of microcalcification in PTC as well as tumorigenesis.
Asunto(s)
Calcinosis/patología , Proteínas de Homeodominio/metabolismo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Apoptosis , Calcinosis/genética , Calcinosis/metabolismo , Proliferación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Proteínas de Homeodominio/genética , Humanos , Invasividad Neoplásica , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Células Tumorales CultivadasRESUMEN
BACKGROUND: Using a large set of genomic data from The Cancer Genome Atlas (TCGA), we classified BRAFwild papillary thyroid carcinomas (PTCs) into 2 subtypes with distinct molecular patterns and different clinical behaviors. We also suggested gene signatures (RAS-score) to predict molecular subtypes and clinical behaviors of BRAFwild PTC. METHOD: Integrated genomic analysis was done using all genomic data of PTC in TCGA data portal (https://tcga-data.nci.nih.gov) and cancer browser (https://genome-cancer.ucsc.edu). Using Gene Ontology and a logistic regression test, we selected gene signatures (RAS-score) and applied this prediction model to the validation cohort (GSE60542). RESULT: When we performed multiplatform genomic analysis, BRAFwild PTCs were divided into 2 molecular subtypes. Each subtype showed distinct molecular patterns and clinical behaviors. Gene signatures successfully predicted molecular subtype in another validation cohort. CONCLUSION: We found that BRAFwild PTCs were divided into 2 molecular subtypes and each subtype showed distinct molecular patterns, different activated pathways, and different clinical behaviors.
Asunto(s)
Mutación , Proteínas Proto-Oncogénicas B-raf/genética , ARN Mensajero/metabolismo , Cáncer Papilar Tiroideo/genética , Bases de Datos Genéticas , Regulación hacia Abajo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Transducción de Señal , Cáncer Papilar Tiroideo/metabolismo , Regulación hacia ArribaRESUMEN
Cellular senescence has been perceived as a barrier against carcinogenesis. However, the senescence-associated secretory phenotype (SASP) of senescent cells can promote tumorigenesis. Here, we show senescent tumour cells are frequently present in the front region of collective invasion of papillary thyroid carcinoma (PTC), as well as lymphatic channels and metastatic foci of lymph nodes. In in vitro invasion analysis, senescent tumour cells exhibit high invasion ability as compared with non-senescent tumour cells through SASP expression. Collective invasion in PTC is led by senescent tumour cells characterized by generation of a C-X-C-motif ligand (CXCL)12 chemokine gradient in the front region. Furthermore, senescent cells increase the survival of cancer cells via CXCL12/CXCR4 signalling. An orthotopic xenograft in vivo model also shows higher lymphatic vessels involvement in the group co-transplanted with senescent cells and cancer cells. These findings suggest that senescent cells are actively involved in the collective invasion and metastasis of PTC.
Asunto(s)
Carcinoma Papilar/patología , Movimiento Celular , Senescencia Celular , Neoplasias de la Tiroides/patología , Animales , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Línea Celular Tumoral , Células Cultivadas , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Femenino , Perfilación de la Expresión Génica , Humanos , Metástasis Linfática , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Células Epiteliales Tiroideas/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Trasplante HeterólogoRESUMEN
BACKGROUND AND OBJECTIVES: Single-incision transaxillary robotic thyroidectomy (START) requires substantial tissue disruption, which produces moderate-to-severe pain in the axilla and neck areas during the early postoperative period. This study aimed to investigate the analgesic effects of ultrasound-guided serratus-intercostal plane blocks and intermediate cervical plexus blocks (CPBs) on the early postoperative pain after START. METHODS: We randomized 22 patients to undergo either ultrasound-guided serratus-intercostal plane and intermediate CPBs (the block group, n = 11) or to not undergo any block (the control group, n = 11). We compared postoperative axillary pain, postoperative neck pain, and analgesic use between the groups during the first 24 hours. The rescue analgesics were intravenous fentanyl (0.5 µg/kg) in the postanesthesia care unit, and intravenous ketorolac tromethamine (30 mg) in the general ward. RESULTS: The block group showed consistently lower pain scores than the control group in the axillary area in the first 24 hours and in the neck area only in the first 3 hours after surgery. The numbers (proportions) of patients who required analgesics were 11 (100%) in the control group and 6 (54.5%) in the block group during the first 24 hours (P = 0.035). No adverse effect was observed related to the peripheral nerve blocks. CONCLUSIONS: After START, a serratus-intercostal plane block performed at the level of the third rib was an effective analgesic technique for axillary pain; however, the clinical effectiveness of intermediate CPB for neck pain may be limited.
Asunto(s)
Bloqueo del Plexo Cervical , Dolor de Cuello/prevención & control , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Procedimientos Quirúrgicos Robotizados/efectos adversos , Tiroidectomía/efectos adversos , Ultrasonografía Intervencional , Adulto , Analgésicos Opioides/administración & dosificación , Bloqueo del Plexo Cervical/efectos adversos , Inhibidores de la Ciclooxigenasa/administración & dosificación , Femenino , Humanos , Ketorolaco Trometamina/administración & dosificación , Masculino , Persona de Mediana Edad , Dolor de Cuello/diagnóstico , Dolor de Cuello/etiología , Bloqueo Nervioso/efectos adversos , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Estudios Prospectivos , República de Corea , Tiroidectomía/métodos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Abnormal wound-healing after thyroidectomy with a resulting scar is a common dermatologic consultation. Despite many medical and surgical approaches, prevention of postoperative scars is challenging. OBJECTIVE: This study validated the efficacy and safety of low-level light therapy (LLLT) using an 830/590 nm light-emitting diode (LED)-based device for prevention of thyroidectomy scars. METHODS AND MATERIALS: Thirty-five patients with linear surgical suture lines after thyroidectomy were treated with 830/590 nm LED-LLLT. Daily application of 60 J/cm (11 minutes) for 1 week starting on postoperative day 1 was followed by treatment 3 times per week for 3 additional weeks. The control group (n = 15) remained untreated. Scar-prevention effects were evaluated 1 and 3 months after thyroidectomy with colorimetric evaluation using a tristimulus-color analyzer. The Vancouver Scar Scale (VSS) score, global assessment, and a subjective satisfaction score (range: 1-4) were also determined. RESULTS: Lightness (L*) and chrome values (a*) decreased significantly at the 3-month follow-up visit in the treatment group compared with those of controls. The average VSS and GAS scores were lower in the treatment group, whereas the subjective score was not significantly different. CONCLUSION: Light-emitting diode based LLLT treatment suppressed the formation of scars after thyroidectomy and could be safely used without noticeable adverse effects.
Asunto(s)
Cicatriz/etiología , Cicatriz/prevención & control , Terapia por Luz de Baja Intensidad , Tiroidectomía/efectos adversos , Pueblo Asiatico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Recently, VE1, a monoclonal antibody against the BRAFV600E mutant protein, has been investigated in terms of its detection of the BRAFV600E mutation. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in thyroid cytology samples is rarely performed, and its diagnostic value in cytology has not been well established. In present study, we explored VE1 immunoexpression in cytology samples from ex vivo papillary thyroid carcinoma specimens in order to minimize limitations of low cellularity and sampling/targeting errors originated from thyroid fineneedle aspiration and compared our results with those obtained using the corresponding papillary thyroid carcinoma tissues. METHODS: The VE1 antibody was evaluated in 21 cases of thyroid cytology obtained directly from ex vivo thyroid specimens. VE1 immunostaining was performed using liquid-based cytology, and the results were compared with those obtained using the corresponding tissues. RESULTS: Of 21 cases, 19 classic papillary thyroid carcinomas had BRAFV600E mutations, whereas two follicular variants expressed wild-type BRAF. VE1 immunoexpression varied according to specimen type. In detection of the BRAFV600E mutation, VE1 immunostaining of the surgical specimen exhibited 100% sensitivity and 100% specificity, whereas VE1 immunostaining of the cytology specimen exhibited only 94.7% sensitivity and 0% specificity. CONCLUSIONS: Our data suggest that VE1 immunostaining of a cytology specimen is less specific than that of a surgical specimen for detection of the BRAFV600E mutation, and that VE1 immunostaining of a cytology specimen should be further evaluated and optimized for clinical use.
RESUMEN
Midkine is a multifunctional, heparin-binding growth factor that is frequently expressed in patients with malignancies but is undetectable in healthy adults. In various cancers, high expression of midkine is associated with aggressive clinical behavior and a poor prognosis. In the present study, we investigated the expression of midkine in papillary thyroid carcinoma (PTC) and assessed its association with a BRAFV600E mutation and the clinicopathological parameters. We determined the presence of a BRAFV600E mutation in 79 cases of PTC and examined the effects of the BRAFV600E mutation on midkine expression in primary thyrocytes. In addition, we evaluated the association between midkine expression and various clinicopathological parameters. We found that midkine is more frequently expressed in BRAFV600E PTC (68.3%) than in BRAF wild-type PTC (18.8%). BRAFV600E transduction could up-regulate midkine expression in primary thyrocytes. Moreover, midkine expression was associated with multiple lymph node (≥5) metastases in BRAFV600E PTC. In conclusion, our results suggest that midkine expression could be a clinically useful marker in predicting the presence of multiple lymph node metastases in BRAFV600E PTC.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma/patología , Metástasis Linfática/patología , Factores de Crecimiento Nervioso/biosíntesis , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/patología , Adulto , Anciano , Western Blotting , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma Papilar , Análisis Mutacional de ADN , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática/genética , Masculino , Persona de Mediana Edad , Midkina , Mutación , Factores de Crecimiento Nervioso/análisis , Polimorfismo de Longitud del Fragmento de Restricción , Reacción en Cadena en Tiempo Real de la Polimerasa , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: We evaluated the utility of the VE1 antibody that can detect a mutant protein resulting from the BRAF V600E mutation as a diagnostic tool for thyroid fine-needle aspiration cytology (FNAC). METHODS: We performed VE1 immunocytochemistry on 202 FNAC specimens from surgically confirmed thyroid nodules. The results were compared with the molecular analyses of the BRAF mutation in these specimens matched with their corresponding histology. RESULTS: Diagnoses of FNAC specimens included benign (9.4%), atypia of undetermined significance/follicular lesion of undetermined significance (11.4%), follicular neoplasm/suspicious for follicular neoplasm (2.0%), suspicious for malignancy (9.4%), and malignancy (65.8%). VE1 immunostaining was positive in 71.3% of FNAC specimens. The overall sensitivity of the VE1 antibody was 88.8%, specificity was 71.2%, positive predictive value was 88.2%, negative predictive value was 72.4%, and diagnostic accuracy was 83.7%. CONCLUSIONS: VE1 immunocytochemistry in thyroid FNAC as a screening test for BRAF mutations is highly specific for malignant category cases but can be suboptimal due to its high false-positive rate for the nonmalignant cases.
Asunto(s)
Anticuerpos Monoclonales , Carcinoma Papilar/patología , Proteínas Proto-Oncogénicas B-raf , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/patología , Adulto , Animales , Biopsia con Aguja Fina , Análisis Mutacional de ADN , Reacciones Falso Positivas , Humanos , Inmunohistoquímica , Ratones , Mutación , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Sensibilidad y EspecificidadRESUMEN
B-RafV600E oncogene mutation occurs most commonly in papillary thyroid carcinoma (PTC) and is associated with tumor initiation. However, a genetic modification by B-RafV600E in thyrocytes results in oncogene-induced senescence (OIS). In the present study, we explored the factors involved in the senescence overcome program in PTC. First of all, we observed down-regulation of p-extracellular signal-regulated kinases 1/2 and up-regulation of dual specific phosphatase 6 (DUSP6) in the PTC with B-RafV600E mutation. DUSP6 overexpression in vitro induced extracellular signal-regulated kinases 1/2 dephosphorylation and inhibited B-RafV600E-induced senescence in thyrocytes. Although DUSP6 protein was degraded by B-RafV600E-induced reactive oxygen species (ROS), thyroid-stimulating hormone (TSH) stabilized DUSP6 protein by increasing Mn superoxide dismutase expression and inhibited B-RafV600E-induced senescence. Although serum TSH was not increased, its receptor was markedly upregulated in PTC with B-RafV600E. Furthermore, TSH together with DUSP6 reactivated Ras signaling, resulted in activation of Ras/AKT/glycogen synthase kinase 3ß, and stabilized c-Myc protein by inhibiting its degradation. These observations led us to conclude that increased TSH signaling overcomes OIS and is essential for B-RafV600E-induced papillary thyroid carcinogenesis.
Asunto(s)
Carcinoma/genética , Senescencia Celular/genética , Fosfatasa 6 de Especificidad Dual/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/genética , Tirotropina/farmacología , Carcinoma/metabolismo , Carcinoma/patología , Carcinoma Papilar , Fosfatasa 6 de Especificidad Dual/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación , Plásmidos/genética , Polimorfismo de Longitud del Fragmento de Restricción , Proteínas Proto-Oncogénicas B-raf/metabolismo , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN , Transducción de Señal/efectos de los fármacos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Tirotropina/sangre , Regulación hacia ArribaRESUMEN
B-RafV600E mutant is found in 40-70% of papillary thyroid carcinoma (PTC) and has an important role in the pathogenesis of PTC. The sodium iodide symporter (NIS) is an integral plasma membrane glycoprotein that mediates active iodide transport into the thyroid follicular cells, and B-RafV600E has been known to be associated with the loss of NIS expression. In this study, we found that B-RafV600E inhibited NIS expression by the upregulation of its promoter methylation, and that specific regions of CpG islands of NIS promoter in B-RafV600E harboring PTC were highly methylated compared with surrounding normal tissue. Although DNA methyltransferase 3a and 3b (DNMT3a,3b) were not increased by B-RafV600E, DNMT1 expression was markedly upregulated in PTC and B-RafV600E expressing thyrocytes. Furthermore, DNMT1 expression was upregulated by B-RafV600E induced NF-κB activation. These results led us to conclude that NIS promoter methylation, which was induced by B-RafV600E, is one of the possible mechanisms involved in NIS downregulation in PTC.
Asunto(s)
Carcinoma/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Regulación Neoplásica de la Expresión Génica , Mutación Puntual , Proteínas Proto-Oncogénicas B-raf/genética , Simportadores/genética , Neoplasias de la Tiroides/genética , Secuencia de Bases , Carcinoma/metabolismo , Carcinoma/patología , Carcinoma Papilar , Células Cultivadas , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/análisis , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN , ADN Metiltransferasa 3A , Regulación hacia Abajo , Humanos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas B-raf/metabolismo , Simportadores/análisis , Simportadores/metabolismo , Cáncer Papilar Tiroideo , Glándula Tiroides/citología , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Regulación hacia ArribaRESUMEN
PURPOSE: We investigated whether (131)I whole-body scintigraphy could predict functional changes in salivary glands after radioiodine therapy. METHODS: We evaluated 90 patients who received initial high-dose (≥3.7 GBq) radioiodine therapy after total thyroidectomy. All patients underwent diagnostic (DWS) and post-ablation (TWS) (131)I whole-body scintigraphy. Visual assessment of salivary radioiodine retention on DWS and TWS was used to divide the patients into two types of groups: a DWS+ or DWS- group and a TWS+ or TWS- group. Salivary gland scintigraphy was also performed before DWS and at the first follow-up visit. Peak uptake and %washout were calculated in ROIs of each gland. Functional changes (Δuptake or Δwashout) of salivary glands after radioiodine therapy were compared between the two groups. RESULTS: Both peak uptake and the %washout of the parotid glands were significantly lower after radioiodine therapy (all p values <0.001), whereas only the %washout were significantly reduced in the submandibular glands (all p values <0.05). For the parotid glands, the TWS+ group showed larger Δuptake and Δwashout after radioiodine therapy than did the TWS- group (all p values <0.01). In contrast, the Δuptake and Δwashout of the submandibular glands did not significantly differ between the TWS+ and TWS- groups (all p values >0.05). Likewise, no differences in Δuptake or Δwashout were apparent between the DWS+ and DWS- groups in either the parotid or submandibular glands (all p values >0.05). CONCLUSION: Salivary gland radioiodine retention on post-ablation (131)I scintigraphy is a good predictor of functional impairment of the parotid glands after high-dose radioiodine therapy.
RESUMEN
Papillary thyroid microcarcinoma (PTMC) has been increasing, without a consensus for the management of this condition. In the present study, we analyzed the clinicopathological features of patients with PTMC to examine the impact of initial therapy and establish appropriate treatment. A total of 2,018 patients with PTMC were enrolled at a single university hospital. Of them, 1,245 patients (61.8%) underwent total thyroidectomy, and 1,838 patients (91.3%) underwent central lymph node (LN) dissection. Five-and 10-yr recurrence rates were 3.2% and 4.6%, respectively. In univariate analysis, the prognostic factors for recurrence were N stage, the number of LN metastases, and extrathyroidal extension. However, multivariate analysis revealed LN metastases and N stage as the only significant prognostic factors after adjusting for confounding factors (P < 0.001). Additionally, multivariate analysis of a subgroup consisting of PTMC patients without N1b revealed the number of central LN metastases as the only significant factor. Therefore, intraoperative examination for central LN metastasis may discriminate high or low risk group.
Asunto(s)
Carcinoma Papilar/patología , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Neoplasias de la Tiroides/patología , Carcinoma Papilar/radioterapia , Carcinoma Papilar/cirugía , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
BACKGROUND: Prophylactic dissection facilitates identification of central lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). Because most staging systems do not stratify risks by the number of LN metastases, postoperative treatments vary among different institutions. Therefore we investigated the significance of number of LN metastases in risk stratification for recurrence in PTC. MATERIAL AND METHODS: A retrospective review was performed for 3,305 patients who had undergone thyroidectomy at Ajou University Hospital. A total of 2,462 patients (73.5 %) underwent total thyroidectomy, and another 3,152 (94.1 %) underwent central LN dissection. Lateral cervical LN dissection had been performed in 420 patients (12.5 %). RESULTS: There were 115 patients with recurrence (3.4 %). Recurrence-free rates were 94.6 % at 5 years and 89.4 % at 10 years. On univariate analysis, prognostic factors for recurrence were extent of thyroidectomy, tumor size, capsular invasion, T stage, N stage, number of LN metastasis, TNM stage, and radioactive iodine (RAI) therapy. On multivariate analysis, number of LN metastasis and N stage were significant prognostic factors for recurrence. Recurrence-free rate was significantly different between patients with 0-1 LN and those with 2 or more LN. CONCLUSIONS: Number of metastatic LN was a significant prognostic factor, in addition to the N stage. Therefore, number of metastatic LN must be considered for postoperative staging system to tailor treatment and follow-up recommendations. In addition, patients with ≥2 metastatic LN may benefit from total thyroidectomy and RAI therapy with postoperative follow-up with serum thyroglobulin.