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.

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 ). 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 ). 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.

Abstract. 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 G 2 phase, characterized by increased cyclin B1 levels and to induce apoptosis by procaspase-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. IntroductionAdrenocortical carcinoma (ACC) is a rare endocrine neoplasia with a variable prognosis, depending on tumor stage and time of diagnosis, but it is generally fatal, with an overall survival of 5 years from detection (1-3). Metastasis associated with ACCs can range from 30 to 85% (4).More recently, elevated or deregulated expression of the c-Myc protein has been detected in a wide range of human cancers, and is often associated with aggressive and poorly differentiated tumors. C-MYC belongs to the class of immediate early genes which are induced in response to a number of mitogenic signals. It encodes a nuclear transcription factor leading to activation or repression of target genes, thus affecting several biological processes, such as cellular growth, differentiation, cell cycle and apoptosis (5,6). Surprisingly, gene expression profile studies have demonstrated an underexpression of C-MYC in ACC compared to adrenocortical adenoma (7-10).The treatment with DNA-damaging agents can sensitize cells to apoptosis when c-Myc is overexpressed (11), but its role in cellular susceptibility to anticancer drugs is controversial. It has been reported that the overexpression of c-Myc not only enhances tumor cell sensitivity (12) but also induces resistance to antineoplastic agents (13).It has been widely demonstrated that cells expressing high c-Myc levels show an apoptosis-prone phenotype in response to different stimuli, affecting cell c...

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