Patient Age Is an Independent Risk Factor of Relapse of Differentiated Thyroid Carcinoma and Improves the Performance of the American Thyroid Association Stratification System.

Background: The 2015 American Thyroid Association (ATA) guidelines proposed a three-category system for estimating the risk of recurrence of differentiated thyroid carcinoma (DTC). This system includes several perioperative features, but not age at diagnosis. However, age has traditionally been recognized as a critical factor in the survival of DTC patients, and the eighth edition of TNM stated that patients older than 55 years were at higher risk of death. In this study, we raised the question of whether age at DTC diagnosis impacts on its risk of recurrence. Specifically, the present study aimed to (i) evaluate the association between age at diagnosis and structural recurrence and (ii) investigate whether age at diagnosis could improve the performance of the ATA system. Methods: During the study period, four institutions selected DTC patients treated with both thyroidectomy and radioiodine and who had follow-up for at least one year. Patients with proven structural evidence of disease during follow-up were identified, and disease-free survival (DFS) was calculated accordingly. Results: The study involved 1603 DTC patients with a median age of 49 years and DFS of 44 months. Disease recurred in 8%. The shortest DFS was found in the oldest patients. The Kaplan-Meier curves were calculated for each decade of age, and there was a significant association with DFS (p = 0.0014). Patients older than 55 years had significantly higher risk (hazard ratio [HR] 1.78, 95% confidence interval [CI 1.23-2.56]). The Kaplan-Meier curves of DFS in high-, intermediate- and low-risk groups showed a significant association only in the high-risk group (p = 0.0058). Patients older than 55 years had significantly higher risk of relapse over time only in the high-risk group (HR 2.15 [CI 2.01-4.53]). Cox's proportional analysis showed that the age cutoff of 55 years and the ATA system were significant predictors of relapse. Adding age at diagnosis above 55 years to the ATA system identified a subgroup of patients at highest risk for relapse. Conclusions: The age threshold adopted in the eighth edition of TNM staging system for DTC patients' prognosis also identifies cases at higher risk of relapse. Applying age at diagnosis, with a cutoff of 55 years, to the ATA risk stratification system identifies cases at highest risk of relapse.

Specific and Non-Specific Biomarkers in Neuroendocrine Gastroenteropancreatic Tumors.

The diagnosis of neuroendocrine tumors (NETs) is a challenging task: Symptoms are rarely specific, and clinical manifestations are often evident only when metastases are already present. However, several bioactive substances secreted by NETs can be included for diagnostic, prognostic, and predictive purposes. Expression of these substances differs between different NETs according to the tumor hormone production. Gastroenteropancreatic (GEP) NETs originate from the diffuse neuroendocrine system of the gastrointestinal tract and pancreatic islets cells: These tumors may produce many non-specific and specific substances, such as chromogranin A, insulin, gastrin, glucagon, and serotonin, which shape the clinical manifestations of the NETs. To provide an up-to-date reference concerning the different biomarkers, as well as their main limitations, we reviewed and summarized existing literature.

Prognosis of patients with differentiated thyroid carcinomas having a preoperative cytological report of indeterminate at low or high risk. A multicenter study.

BACKGROUND: Italian cytology system for thyroid fine-needle aspiration (FNA) includes indeterminate lesions at low- (Tir 3A) and high-risk (Tir 3B). The present retrospective multicenter study was undertaken to compare the histological type of cancers and disease-free survival in these two groups. METHODS: Eight institutions participated. Thyroid cancer patients diagnosed and followed-up after Tir 3A or Tir 3B were reviewed. Histological diagnosis was adopted as the gold standard. Patients were defined with cancer recurrence or no evidence of disease. Disease-free survival (DFS) was calculated. A non-parametric statistical analysis was used. DFS was estimated by Kaplan-Meier method and Hazard Ratio (HR) defined the slope of curves. RESULTS: Two hundred and nine patients (median DFS 24 months) were enrolled and a 6.3% of these recurred. Tir 3B group had higher age (p = 0.014), larger cancer size (p = 0.0002), shorter DFS (p = 0.003), higher number of aggressive cancers (p = 0.006), and relapse frequency double than Tir 3A. At survival curves analysis, Tir 3B group had HR of 2.37 with respect to Tir 3A. At Cox's proportional hazard regression analysis histology was the only significant predictor of relapse. CONCLUSIONS: While patients with thyroid FNA of Tir 3B should be addressed to surgery due to high likelihood of more aggressive cancer, a diagnostic surgery could be avoided in patients with Tir 3A if concurrent unsuspicious clinical features are found.

C-MYC modulation induces responsiveness to paclitaxel in adrenocortical cancer cell lines.

C-MYC is overexpressed in many types of cancer linked to poor prognosis. We examined the c-Myc protein expression in adrenocortical cancer (ACC) cells to investigate the role of this protein in the neoplasm, its involvement in chemotherapy and finally to determine whether c-Myc could be considered a prognostic factor in patients with ACC. H295R and SW13 cell lines were treated with paclitaxel. c-Myc overexpressing cell clones were achieved by transfecting the H295R cell line with the pcDNA3-hMYC plasmid expressing the full-lengh C-MYC coding sequence. The SW13 cell line was transfected with siRNA oligonucleotides for C-MYC. Cell cycle analysis was evaluated by flow cytometry. c-Myc, cyclin B1 and pro caspase expression levels were evaluated by western blot analysis. We found that expression of c-Myc was highly expressed in the SW13 cells, whereas the protein was undetectable in the H295R cells. Different doses of paclitaxel were required in the two ACC cell line to induce a block in the G2 phase, characterized by increased cyclin B1 levels and to induce apoptosis by pro-caspase-3 activation. Interestingly, the silencing of C-MYC mRNA prevented paclitaxel induced apoptosis in SW13 cells, whereas in the H295R cells the overexpression of C-MYC rendered the cells more prone to growth inhibition after paclitaxel exposure. The present study directly demonstrates that C-MYC plays a central role in controlling proliferation in ACC cells after paclitaxel treatment and that c-Myc could be considered as a marker for predicting response to chemotherapeutic agents in ACC cell lines.