How do and promoter mutations interact with the ATA and TNM staging systems in thyroid cancer?

CONTEXT

The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). and promoter mutations have been shown to correlate with the histopathological features and outcome of DTC. Our objectives were to study the correlation of these molecular markers with these clinicopathological-staging systems.

PATIENTS AND METHODS

We studied 296 unselected patients, 214 females and 82 males with a median age of 36 years (IQR 23.3-49.0). and promoter mutations were tested by PCR-based Sanger sequencing. Data were extracted from medical records and analysed using Chi-Square and Fisher Exact tests and Kaplan Meier analysis.

RESULTS

Of 296 patients tested, 137 (46.3%) had -positive tumors and 72 (24.3%) were positive for promoter mutations. The mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of persistent disease (PD) ( 0.12). Unlike , promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.006) and in TNM stages III and IV than lower stages (0.0001). promoter mutations also predicted the outcome, being present in 37.2% of patients with PD compared to only 15.4% in those without evidence of disease (0.0001). The same pattern was also seen when and promoter mutations were combined.

CONCLUSION

promoter mutations alone or in combination with mutation, but not mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems.