MRNA Expression As a Novel Prognostic Marker in Papillary Thyroid Carcinomas
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Telomerase reverse transcriptase () promoter mutations have been found in a subset of papillary thyroid carcinomas (PTCs) and are associated with tumor aggressiveness and worse prognosis. However, little is known about the status of mRNA expression and its relationship between promoter mutations and clinicopathological features. We analyzed 159 PTC samples for promoter mutations using direct DNA sequencing. expression was measured using quantitative reverse transcription polymerase chain reaction. To examine low allelic frequency of promoter mutations with high sensitivity, we used droplet digital polymerase chain reaction (ddPCR). The relationship between the status of the promoter mutation/expression and clinicopathological features including recurrence risk was statistically analyzed. promoter mutations were found in 20 cases (12.6%). However, expression was observed not only in the mutation-positive tumors but also in 56 of 139 (40.3%) mutation-negative tumors. Among them, we detected low allelic frequency of promoter mutations in three samples (5.4%) using ddPCR. We confirmed a significant association between promoter mutations and aggressive clinicopathological features in this series. The risk of recurrence of mutation-negative/expression-positive tumors was significantly higher than that of the mutation-negative/expression-negative tumors, suggesting that expression even in absence of a mutation confers a negative influence on PTCs. Moreover, when we reclassified the mutation-negative cases into two groups based on the expression levels: expression-negative/expression levels <80th percentile and expression levels >80th percentile because minimal expression may have a negligible clinical impact, a higher hazard ratio for recurrence was observed. Interestingly, expression levels in the mutation-negative PTCs were inversely correlated with patient age and the presence of mutations. We confirm a strong correlation between the presence of promoter mutations and aggressive clinicopathological features in this PTC series. In addition, there were PTCs showing high mRNA expression even in the absence of promoter mutations. These cases also showed a significantly higher recurrence rate. Since the promoter mutations are observed only in elderly patients, mRNA expression can be a useful prognostic marker especially in younger PTC patients.
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