Novel Prognostic Factors Associated with Cell Cycle Control in Sporadic Medullary Thyroid Cancer Patients.

Background: Medullary thyroid cancer (MTC) is a rare neuroendocrine-derived malignancy. It is represented by sporadic and familiar forms, and both can have oncogene mutations. Numerous markers can be used to define MTC; however, none is generally approved for predicting the outcome of sporadic MTC.

Aim: The aim of this work was to analyze PTTG1/securin and Aurora kinase A expressions in MTC patients, both at the gene and protein levels, and to define their prognostic role in MTC assessing their association with lab and clinical parameters.

Patients And Methods: Seventy-one sporadic MTC human samples were analyzed for mutations and by qPCR for and (Aurora kinase A) expression. Ki-67 levels and western blot reactivity for PTTG1 and Aurora kinase A were also determined in a selected cohort of patients.

Results: somatic mutations were found in 48% of the patients (34/71). expression was statistically different among the groups with or without regional lymph node metastasis ( < 0.0001) and advanced stage disease ( < 0.01). and expressions were statistically higher than those of controls ( = 0.01 and < 0.002, respectively). expression and Ki-67 levels were statistically different among the groups with remitted or persistent disease ( < 0.05 and < 0.01, respectively). We found a significant correlation between the expressions of and ( < 0.0002, = 0.5298) and between the expressions of and Ki-67 ( = 0.01). Ki-67 levels were statistically different among the groups with or without metastatic lymph nodes ( = 0.01) or distant metastases ( = 0.003).

Conclusion: The presence of an altered expression of and is a negative prognostic factor associated with a more aggressive course of disease, such as an advanced stage or disease persistence. It emerges as a cell cycle process mediated by the 2 factors, in addition to the RET pathway, which can be altered in MTC patients.