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The incidence of papillary thyroid cancer (PTC) is rapidly growing, the recorded increase being mainly related to tumors ≤2 cm. The re-classification of tumors >1 and ≤2 cm limited to the thyroid from the T2 to the T1 category triggered some concerns about their best management. In order to identify possible predictors of disease outcome, several clinico-pathological features were analyzed by uni- and multivariate analyses in a retrospective consecutive series of 251 PTCs ≤2 cm. Moreover, since 37% of cases were submitted to prophylactic central compartment node dissection (CLND, VI–VII levels) and radioiodine ablation was performed only when the tumor had an extrathyroidal extension, the impact of these therapeutic tools on the final outcome was evaluated. Among all outcome predictors analyzed, only lymph node metastases and extracapsular invasion were strongly associated with persistence/recurrence. It is worth noting that neither age nor tumor size was a significant indicator of the outcome. Interestingly, as far as the therapeutic interventions are concerned, CLND was strongly associated with remission, whereas radioiodine ablation did not influence the outcome. In conclusion, present results confirm the prognostic influence of node metastases and extra-thyroidal invasion, indicating the need for aggressive treatment in tumors extending beyond the capsule. On the contrary, all pT1N0 tumors, regardless of the diameter, the number of intrathyroidal foci, and the age can be effectively treated only by surgery. The major impact of prophylactic CLND on prognosis suggests to routinely associate it to total thyroidectomy in cases with a preoperative diagnosis of malignancy.
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Department of Clinical Sciences and Community Health, Endocrine Unit Fondazione IRCCS Ca' Granda, Endocrine Surgery Unit, Fondazione IRCCS Ca' Granda, Unit of Pathological Anatomy, Department of Health Science, University of Milan, Milan, Italy
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Department of Clinical Sciences and Community Health, Endocrine Unit Fondazione IRCCS Ca' Granda, Endocrine Surgery Unit, Fondazione IRCCS Ca' Granda, Unit of Pathological Anatomy, Department of Health Science, University of Milan, Milan, Italy
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Department of Clinical Sciences and Community Health, Endocrine Unit Fondazione IRCCS Ca' Granda, Endocrine Surgery Unit, Fondazione IRCCS Ca' Granda, Unit of Pathological Anatomy, Department of Health Science, University of Milan, Milan, Italy
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Department of Pathophysiology and Transplantation, University of Milan, Milan, Ital
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Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
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Department of Medical Oncology, University of Milan, Milan, Italy
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Department of Pathophysiology and Transplantation, University of Milan, Milan, Ital
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This study aimed to identify circulating miRNAs as novel non-invasive biomarkers for prognosis and vandetanib response in advanced medullary thyroid cancer (MTC) patients. We prospectively recruited two independent cohorts of locally advanced/metastatic MTC patients including a subgroup of vandetanib-treated subjects: a discovery cohort (n = 20), including matched plasma/tissue samples (n = 17/20), and a validation cohort, yielding only plasma samples (n = 17). Plasma samples from healthy subjects (n = 36) and MTC patients in remission (n = 9) were used as controls. MTC (n = 17 from 8 patients included in discovery cohort) and non-neoplastic thyroid specimens (n = 3) were assessed by microarray profiling to identify candidate circulating miRNAs. qRT-PCR and in situ hybridization were carried out to validate the expression and localization of a selected miRNA within tissues, and qRT-PCR was also performed to measure miRNA levels in plasma samples. By microarray analysis, we identified 51 miRNAs differentially expressed in MTC. The most overexpressed miR, miR-375, was highly expressed by C cells compared to other thyroid cells, and more expressed in MTC than in reactive C-cell hyperplasia. MTC patients had significantly higher miR-375 plasma levels than healthy controls (P < 0.0001) and subjects in remission (P = 0.0004) as demonstrated by qRT-PCR analysis. miR-375 plasma levels were not predictive of vandetanib response, but, notably, high levels were associated with significantly reduced overall survival (HR 10.61, P < 0.0001) and were a strong prognostic factor of poor prognosis (HR 6.24, P = 0.00025) in MTC patients. Overall, our results unveil plasma miR-375 as a promising prognostic marker for advanced MTC patients, to be validated in larger cohorts.
