Molecular profiling for acromegaly treatment: a validation study.

Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >2<3 SDS or >3 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P < 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.

Pasireótida en acromegalia por tumores agresivos, descripción de 4 casos. Hacia una medicina personalizada / Pasireotide in acromegaly by aggressive tumors, description of four clinical cases. Towards a personalized medicine

No disponible

Graves' disease TSHR-stimulating antibodies (TSAbs) induce the activation of immature thymocytes: a clue to the riddle of TSAbs generation?

Graves' disease (GD) is an autoimmune thyroid disease defined by the production of stimulating autoantibodies to the thyroid-stimulating hormone receptor (TSHR) (TSAbs) that induce a sustained state of hyperthyroidism in patients. We previously demonstrated that TSHR, the target of this autoimmune response, is also a key susceptibility gene for GD, probably acting through thymic-dependent central tolerance. We also showed that TSHR is, unexpectedly, expressed in thymocytes. In this report, we confirm the expression of TSHR in thymocytes by protein immunoblotting and quantitative PCR, and show that expression is confined to maturing thymocytes. Using functional assays, we show that thymic TSHR is functional and that TSAbs can stimulate thymocytes through this receptor. This new activity of TSAbs on thymocytes may: 1) explain GD-associated thymic enlargement (hyperplasia), and 2) suggest the provocative hypothesis that the continuous stimulation of thymocytes by TSAbs could lead to a vicious cycle of iterative improvement of the affinity and stimulating capability of initially low-affinity antibacterial (e.g., Yersinia) Abs cross-reactive with TSHR, eventually leading to TSAbs. This may help to fill one of the gaps in our present understanding of unusual characteristics of TSAbs.

Preoperative TSH level and risk of thyroid cancer in patients with nodular thyroid disease: nodule size contribution / Niveles preoperatorios de TSH y riesgo de cáncer de tiroides en pacientes con enfermedad nodular tiroidea: contribución del tamaño del nódulo

BACKGROUND: Many reports have supported the relationship between high preoperative TSH levels and risk of thyroid cancer in nodular thyroid disease (NTD). OBJECTIVES: We investigated whether TSH levels are related to the risk of differentiated thyroid carcinoma (DTC) in patients who have undergone total thyroidectomy for NTD. The relationship between TSH and size of malignant nodule was investigated. Finally, we assessed whether TSH levels are related to DTC and presence of additional benign nodules. PATIENTS AND METHODS: A retrospective study of 980 patients was conducted. Variables included age at diagnosis, TSH level, nodule size, gender, final histology (benign versus DTC), and type of malignancy. RESULTS: Malignancy was present in 261 (26.6%) patients. These patients had higher median TSH levels as compared to those with no malignancy (1.61mU/L (0.9-2.5) versus 0.9 mU/L (0.3-1.6); p-value < 0.001). TSH was higher in patients with DTC in whom the largest nodule was malignant than in patients in whom the largest nodule was benign (1.80mU/L (1.1-2.6) versus 1.38mU/L (0.7-2.1) respectively; p-value = 0.025). A significant correlation was seen between malignant nodule size and TSH level, but not between TSH levels and size of the largest benign nodule. CONCLUSIONS: Our study supported an association between preoperative TSH levels and risk of DTC in patients with NTD. There was also a direct relationship between malignant nodule size and TSH levels. By contrast, no relationship was found between the size of benign nodules and TSH levels

ANTECEDENTES: Un gran número de artículos han confirmado la relación entre los niveles elevados de TSH preoperatoria y el riesgo de cáncer de tiroides en la enfermedad nodular tiroidea (ENT). OBJETIVOS: Analizamos si los valores de TSH preoperatoria se relacionan con el riesgo de cáncer diferenciado de tiroides (CDT) en pacientes tiroidectomizados por ENT. Además, investigamos la relación entre TSH y el tamaño del nódulo maligno. Finalmente, valoramos si la TSH se relaciona con la presencia de CDT y con la presencia de nódulos benignos adicionales. PACIENTES Y MÉTODOS: Se estudiaron retrospectivamente 980 pacientes. Las variables consideradas fueron: edad al diagnóstico, sexo, valor de TSH, tamaño del nódulo, histología definitiva y tipo de CDT. RESULTADOS: En 261 (26,6%) casos el diagnóstico fue de CDT. Estos pacientes tenían niveles más elevados de TSH que los pacientes con histología benigna (mediana de 1,61 mU/l [0,9-2,5] versus 0,9 mU/l [0,3-1,6]; p < 0,001). La TSH fue más elevada en pacientes con CDT en los que el nódulo dominante fue maligno en relación con los que el nódulo dominante fue benigno (1,80 mU/l [1,1-2,6] versus 1,38 mU/l [0,7-2,1], p = 0,025). Hubo una correlación significativa entre el tamaño del nódulo maligno y la TSH, pero no entre la TSH y el tamaño del nódulo benigno dominante. CONCLUSIONES: Confirmamos la asociación entre los niveles preoperatorios de TSH y el riesgo de CDT en la ENT. Describimos una relación directa entre el tamaño del nódulo maligno y los valores de TSH. Esta relación no se confirma para el tamaño de los nódulos benignos adicionales

El tratamiento con estatinas no influye en la forma de presentación del carcinoma diferenciado de tiroides / Statin therapy does not influence in the form onset of differentiated thyroid carcinoma

No disponible

Preoperative TSH level and risk of thyroid cancer in patients with nodular thyroid disease: nodule size contribution.

BACKGROUND: Many reports have supported the relationship between high preoperative TSH levels and risk of thyroid cancer in nodular thyroid disease (NTD). OBJECTIVES: We investigated whether TSH levels are related to the risk of differentiated thyroid carcinoma (DTC) in patients who have undergone total thyroidectomy for NTD. The relationship between TSH and size of malignant nodule was investigated. Finally, we assessed whether TSH levels are related to DTC and presence of additional benign nodules. PATIENTS AND METHODS: A retrospective study of 980 patients was conducted. Variables included age at diagnosis, TSH level, nodule size, gender, final histology (benign versus DTC), and type of malignancy. RESULTS: Malignancy was present in 261 (26.6%) patients. These patients had higher median TSH levels as compared to those with no malignancy (1.61 mU/L (0.9-2.5) versus 0.9 mU/L (0.3-1.6); p-value<0.001). TSH was higher in patients with DTC in whom the largest nodule was malignant than in patients in whom the largest nodule was benign (1.80 mU/L (1.1-2.6) versus 1.38 mU/L (0.7-2.1) respectively; p-value=0.025). A significant correlation was seen between malignant nodule size and TSH level, but not between TSH levels and size of the largest benign nodule. CONCLUSIONS: Our study supported an association between preoperative TSH levels and risk of DTC in patients with NTD. There was also a direct relationship between malignant nodule size and TSH levels. By contrast, no relationship was found between the size of benign nodules and TSH levels.

Evolution of differentiated thyroid cancer: a decade of thyroidectomies in a single institution.

BACKGROUND: Numerous studies have shown an increase in the incidence of thyroid cancer (TC) in recent years. OBJECTIVES: In this paper, we reviewed the incidence of TC in a series of patients undergoing thyroid surgery at a single institution over a 10-year period. PATIENTS AND METHODS: The cohorts were divided into two periods (2001-2005 and 2006-2010) with the purpose of comparing various clinicopathologic variables. RESULTS: A total of 1,263 patients were included. A significant increase in the number of malignancies was shown in the second period, namely 90 cases in 2001-2005 (15.2% of all interventions) compared to 163 cases in 2006-2010 (24.3%) (p < 0.001). These differences were attributed to an increase in papillary thyroid carcinoma (PTC), as there were 66 PTC cases in the first period (11.13% of thyroidectomies performed) compared to 129 cases in the second period (19.25%). There were no clinicohistological differences among PTC cases in these two periods. CONCLUSIONS: Over the last decade, there has been an increase in the incidence of TC in patients undergoing thyroid surgery. This increase is exclusively due to increases in PTC. Our study verifies the existence of this trend in our geographical area, similar to that noted in other parts of the world.

Alteraciones del metabolismo hidrocarbonado en la acromegalia / Abnormalities of carbohydrate metabolism in acromegaly

Fundamento y objetivo: Hasta un 50% de los pacientes con acromegalia presentan alteraciones en el metabolismo hidrocarbonado (AMHC). La evolución natural de la enfermedad y las distintas alternativas terapéuticas impactan de forma diferente en esta predisposición. El objetivo de este trabajo fue valorar la prevalencia, las características de los pacientes y el efecto de los distintos tratamientos en la AMHC en los pacientes acromegálicos de nuestro centro. Pacientes y método: Se realizó un estudio transversal que incluyó a 55 pacientes con acromegalia. Se analizaron: edad, sexo, índice de masa corporal (IMC), factor de crecimiento insulínico tipo 1 (IGF-1), tamaño tumoral, tratamientos, y presencia de diabetes mellitus (DM) y grado de control metabólico inicial y tras las distintas alternativas terapéuticas. Resultados: De los 55 pacientes estudiados, el 54% eran varones, con una edad media (DE) de 50 (17) años y un IMC de 27,9 (3,8) kg/m2. Las AMHC estaban presentes en el 50,9% (n = 28) (DM en el 24% y glucosa basal alterada en el 27%). Los pacientes con DM no presentaban diferencias en el IMC, la edad ni el IGF-1 inicial respecto a los que no tenían DM. Sin embargo, presentaban más macroadenomas. En los pacientes diabéticos, la hemoglobina glucosilada (HbA1c) descendió después de la cirugía de 7,6 a 6,7% y después de los análogos de la somatostatina de 7,1 a 6,6%, pero solo con pegvisomant hemos observado una reducción significativa de HbA1c: del 9,8 al 5,6% (p < 0,05). Es más, solo pegvisomant ha permitido disminuir la intensidad del tratamiento hipoglucemiante. Conclusiones. La prevalencia de AMHC supera al 50% de los casos y se correlaciona con el tamaño tumoral. No hemos observado diferencias en el control glucémico en los pacientes tratados con las diferentes alternativas terapéuticas, excepto en el grupo que recibió pegvisomant, que logró una mejoría del mismo, junto con una reducción del tratamiento hipoglucemiante (AU)

Background and objective: Carbohydrate metabolism (CHM) is impaired in over 50% of acromegalic patients. Natural history of acromegaly and treatment modalities may impact in a different way on CHM. We assessed CHM alterations in acromegaly and their relationship with clinical features and treatment options. Patients and method: Retrospective study with 55 patients with acromegaly. Age, sex, body mass index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were analyzed before and after surgery or medical treatment. Results: There were 30 men and 25 women. Mean age was 50 17 years and mean BMI was 27.9 3.8 Kg/ m2. Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels between IFG/DM and patients without CHM impairment. However, IFG/DM patients had macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant group, insulin and/or oral agents had to be lowered. Conclusions: Up to 50% of patients with active acromegaly have CHM impairment which correlates with tumor size. Only pegvisomant is associated with significant improvement in glycemic control and a reduction in hypoglycemic treatment (AU)

[Abnormalities of carbohydrate metabolism in acromegaly]. / Alteraciones del metabolismo hidrocarbonado en la acromegalia.

BACKGROUND AND OBJECTIVE: Carbohydrate metabolism (CHM) is impaired in over 50% of acromegalic patients. Natural history of acromegaly and treatment modalities may impact in a different way on CHM. We assessed CHM alterations in acromegaly and their relationship with clinical features and treatment options. PATIENTS AND METHOD: Retrospective study with 55 patients with acromegaly. Age, sex, body mass index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were analyzed before and after surgery or medical treatment. RESULTS: There were 30 men and 25 women. Mean age was 50 ± 17 years and mean BMI was 27.9 ± 3.8 Kg/m(2). Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels between IFG/DM and patients without CHM impairment. However, IFG/DM patients had macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant group, insulin and/or oral agents had to be lowered. CONCLUSIONS: Up to 50% of patients with active acromegaly have CHM impairment which correlates with tumor size. Only pegvisomant is associated with significant improvement in glycemic control and a reduction in hypoglycemic treatment.

Low frequency of GITR+ T cells in ex vivo and in vitro expanded Treg cells from type 1 diabetic patients.

Reported alterations in T(reg) cells from type 1 diabetes (T1D) patients led us to a revision of their phenotypical features compared with controls. A fine cytometric analysis was designed for their characterization, using a panel of markers including FOXP3, CTLA4, glucocorticoid-induced TNFR family related (GITR) and CD127. The frequency of peripheral CD4(+)CD25(hi) T(reg) cells was similar between samples. However, the yield of sorted T(reg) cells was significantly lower in patients than in controls. When comparing the T(reg)-cell phenotype between samples, the only difference concerned the expression of GITR. A significant decrease of GITR(+) cells and GITR mean fluorescence intensity within the T(reg)-cell population, and to a lesser extent in the effector population, was observed in T1D compared with controls. Moreover, GITR expression was analyzed in several conditions of T-cell activation and differences were only observed in T1D T(reg) cells versus controls when responding to sub-optimal stimulation, that is, soluble anti-CD3 or medium alone but not in the presence of anti-CD3-/anti-CD28-coated beads. However, expanded T1D T(reg)-cell-mediated suppression was as efficient as that mediated by their control counterparts, showing no association between their regulatory capacity and the reduced GITR. Our results show a higher susceptibility to apoptosis in patients' versus controls' T(reg) cells, suggesting that GITR is a T(reg)-cell marker that would be primarily involved in T(reg)-cell survival rather than in their suppressor function.

Second primary cancer in patients with papillary thyroid carcinoma.

BACKGROUND AND AIM: There is an increased incidence of secondary primary cancer (SPC) in patients with papillary thyroid carcinoma (PTC). The risk is stronger in the first year after the first malignancy (synchronous tumours). The aim of this study was to assess the prevalence of SPC in patients with PTC, and to analyse whether the timing of tumour presentation influenced the clinicopathological characteristics of PTC. PATIENTS AND METHODS: A total of 184 patients with PTC were included in the study. RESULTS: There were 24 patients with SPC and nine with PTC and two other primary tumours (42 additional malignancies in total). Additional tumours were more prevalent in male and older patients. In 11 cases (33%), the two carcinomas were synchronous. PTCs from synchronous cases were significantly larger than those from non-synchronous cases. CONCLUSION: Patients with PTC were at elevated risk for SPC. In one third of patients, both neoplasms were diagnosed within the same year. Male and older patients were more likely to have SPC.

Sorafenib in metastatic thyroid cancer.

Although thyroid cancer usually has an excellent prognosis, few therapeutic options are available in the refractory setting. Based on the recent results of phase II studies with tyrosine kinase inhibitors, we designed a retrospective analysis of patients with metastatic thyroid cancer treated with sorafenib in seven Spanish referral centers. Consecutive patients with progressive metastatic thyroid cancer (papillary, follicular, medullary, and anaplastic) not suitable for curative surgery, radioactive-iodine therapy, or radiotherapy were treated with sorafenib 400 mg twice a day. The primary end point was objective response rate (RR). Secondary end points included toxicity, median progression-free survival (mPFS), median overall survival (mOS), and correlation between tumor marker levels (thyroglobulin, calcitonin, and carcinoembryonic antigen) and efficacy. Between June 2006 and January 2010, 34 patients were included in the study. Sixteen patients presented differentiated thyroid carcinomas (DTC) of which seven (21%) were papillary, nine (26%) follicular, 15 (44%) medullary (MTC), and three (9%) were anaplastic (ATC). Eleven (32%) patients achieved partial response and 14 (41%) had stable disease beyond 6 months. Regarding histological subtype, RRs were 47% (seven of 15) for MTC, 19% (three of 16) for DTC, and 33% (one of three) for ATC. With a median follow-up of 11.5 months, mPFS were 13.5, 10.5, and 4.4 months for DTC, MTC, and ATC respectively. Tumor markers were evaluated in 22 patients, and a statistically significant association was observed between RR and decrease in tumor marker levels >50% (P=0.033). In this retrospective trial, sorafenib showed antitumor efficacy in all histological subtypes of thyroid cancer, warranting further development in this setting.

Preoperative thyrotropin serum concentrations gradually increase from benign thyroid nodules to papillary thyroid microcarcinomas then to papillary thyroid cancers of larger size.

We evaluated the preoperative serum thyrotropin (TSH) levels in 386 patients operated on for nodular thyroid disease (NTD). TSH levels for cases with final benign disease and differentiated thyroid carcinoma (DTC) were compared. No evidence of cancer was detected in 310 patients (80.3%), whereas malignancy was present in 76 cases (19.7%). Mean TSH concentration was 1.36 ± 1.62 mU/L in benign patients and 2.08 ± 2.1 in cases with malignant lesions (P = 0.0013). The group of malignancy was subdivided in papillary thyroid carcinoma (PTMC) versus thyroid cancer of larger size (TCLS). Mean TSH was 1.71 ± 1.52 in PTMC and 2.42 ± 2.5 in TCLS. Significant differences were found when all groups (benign, PTMC and TCLS) were compared (P < 0.001). However, pairwise comparisons between them showed that differences were only significant between benign and TCLS groups (P < 0.01). In conclusion, TSH levels were higher in patients with a final diagnosis of DTC. Moreover, it appears that there exists an increment in tumor size as a function of increment in the TSH level.

[Usefulness of the immunohistochemical analysis of several molecular markers in the characterization of papillary thyroid carcinoma with initial lymph node metastasis]. / Utilidad del análisis inmunohistoquímico de diversos marcadores moleculares en la caracterización del carcinoma papilar de tiroides con metástasis linfáticas iniciales.

INTRODUCTION AND OBJECTIVE: Regional lymph node metastases (LNM) are a common finding in papillary thyroid cancer (PTC). Approximately half of patients have LNM at diagnosis. The aim of this study was to analyze immunohistochemically the combined expression of different PTC-related molecules in order to identify cases with a tendency to show LNM. PATIENTS AND METHODS: Thirty-five patients were included in the study. The patients were distributed in two groups. Group I included 19 patients with no histological evidence of LNM at diagnosis. Group II included 16 patients with histological evidence of cervical LNM. Samples were stained for RET/PTC, EGFR, p16(INk4a), p21(cip1), p27(kip1), BCL2, and pAKT. RESULTS: Expression of p21(cip1), p27(kip1), p16(INk4a), Bcl-2, and pAKT showed no differences between the two groups. However, RET/PTC and EGFR expression showed significant differences: in both cases, staining was more frequent in patients with LNM. Simultaneous positivity of RET/PTC and EGFR was a discriminative marker in patients with LNM. Finally, the combination of RET/PTC negative, EGFR negative and p16(INk4a) negative was found in none of the patients with LNM but in nearly half of those in group I. CONCLUSIONS: Immunohistochemical analysis of several molecular markers could be useful in the phenotypic characterization of PTC. Application of these markers could enhance diagnosis and improve the management of patients with thyroid cancer.

Utilidad del análisis inmunohistoquímico de diversos marcadores moleculares en la caracterización del carcinoma papilar de tiroides con metástasis linfáticas iniciales / Usefulness of the immunohistochemical analysis of several molecular markers in the characterization of papillary thyroid carcinoma with initial lymph node metastasis

Introducción y objetivo En el carcinoma papilar de tiroides, la detección de metástasis linfáticas (ML) en la región cervical es frecuente, observándose en cerca de la mitad de los casos en el momento del diagnóstico. El objetivo del estudio es analizar mediante técnica inmunohistoquímica la expresión combinada de diversas moléculas con el fin de establecer las características de aquellos casos con mayor tendencia a desarrollar ML. Pacientes y métodos Treinta y cinco pacientes con carcinoma papilar de tiroides fueron distribuidos en 2 grupos. El grupo i incluyó 19 pacientes que no presentaron ML al diagnóstico. En el grupo ii se incluyeron 16 pacientes en los cuales se había demostrado la presencia de ML. En todos los casos se practicó tinción inmunohistoquímica para RET/PTC, receptor del factor de crecimiento epidérmico (EGFR), p16INk4a, p21cip1, p27kip1, BCL2 y pAKT. Resultados No se apreciaron diferencias en ambos grupos en relación a p21cip1, p27kip1, p16INk4a, Bcl-2 y pAKT. No obstante, se observaron diferencias de expresión para RET/PTC y para EGFR, siendo ambas más frecuentes en los pacientes con ML. Asimismo se vio que la doble positividad de RET/PTC y el EGFR discriminaba de manera significativa los casos con ML. Finalmente, la triple combinación: RET/PTC negativo, EGFR negativo y p16INk4a negativo no se daba en ningún paciente del grupo ii y en casi la mitad del grupo i. Conclusiones El estudio de la expresión de diversas moléculas de manera combinada puede resultar eficaz en la caracterización fenotípica del carcinoma papilar de tiroides. Con ello se podría mejorar el manejo de los pacientes con cáncer de tiroides (AU)

Introduction and objective Regional lymph node metastases (LNM) are a common finding in papillary thyroid cancer (PTC). Approximately half of patients have LNM at diagnosis. The aim of this study was to analyze immunohistochemically the combined expression of different PTC-related molecules in order to identify cases with a tendency to show LNM. Patients and methods Thirty-five patients were included in the study. The patients were distributed in two groups. Group I included 19 patients with no histological evidence of LNM at diagnosis. Group II included 16 patients with histological evidence of cervical LNM. Samples were stained for RET/PTC, EGFR, p16INk4a, p21cip1, p27kip1, BCL2, and pAKT. Results Expression of p21cip1, p27kip1, p16INk4a, Bcl-2, and pAKT showed no differences between the two groups. However, RET/PTC and EGFR expression showed significant differences: in both cases, staining was more frequent in patients with LNM. Simultaneous positivity of RET/PTC and EGFR was a discriminative marker in patients with LNM. Finally, the combination of RET/PTC negative, EGFR negative and p16INk4a negative was found in none of the patients with LNM but in nearly half of those in group I. ConclusionsI mmunohistochemical analysis of several molecular markers could be useful in the phenotypic characterization of PTC. Application of these markers could enhance diagnosis and improve the management of patients with thyroid cancer (AU)

Differences in the Form of Presentation between Papillary Microcarcinomas and Papillary Carcinomas of Larger Size.

Papillary thyroid carcinomas (PTCs) with a diameter ≤1 cm are referred to as papillary microcarcinomas (PTMCs). The prognostic factors for PTMCs have not been defined. Different clinical and histopathologic variables were studied in 152 PTCs, including 74 PTMCs and 78 PTCs of larger size. We found that PTMCs are associated with less multifocality (P = .046) and bilaterality (P = .003), fewer lymphadenectomies (P < .001), and a higher rate of incidental tumours (P < .001). Moreover, patients with a low aggressive profile were significantly older than the remaining patients (54 ± 13.7 years versus 45.8 ± 13.1 years; P = .001). In conclusion PTMCs show significant differences compared to PTCs of larger size in the form of presentation. Furthermore, it is possible that the classic risk factors, which are well validated in PTCs, such as age, must be cautiously interpreted in the current increasing subgroup of PTMCs.

Targeted therapies in thyroid cancer.

Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations that characterize tumor growth has provided novel targets in cancer therapy. Several proteins have been implicated as having a crucial role in the carcinogenesis of differentiated thyroid cancer, such as those involved in RET/PTC-RAS-RAF-MAPK pathway. Moreover, vascular aberrations and angiogenesis equilibrium have also been related to tumor growth. The development of new, targeted therapies and their encouraging initial results have opened a hopeful opportunity of treatment for these orphan therapy tumor patients.