2015 HSC Section 1 Book of Articles
MACIS score > 4.0 was associated with aggressive PTC. 22 We did not find a difference in BRAF V600E mutations between patients with a MACIS score < 4, and with scores of 4 or greater (60% vs. 25%, P 5 .56). Overall MACIS score showed a trend toward negative association with the BRAF V600E mutation ( P 5 .087). In adults, BRAF V600E has been shown to be a useful prognostic indicator when added to MACIS 23 ; however, another study 24 failed to show a statistical association between a MACIS score of > 6 (which is commonly used as a cutoff for aggressive disease in adults) and the pres- ence of the BRAF mutation. No studies previous per- formed in children with the BRAF V600E mutation have reviewed association with MACIS score. Children typically present with higher rates of regional metastases (57% in one study 2 ) than adults (13% in one study 25 ). Two other studies in children examined the presence of lymphatic metastases 14 and tumor size, lymph node invasion, distant metastases, and extrathyroidal extension, 11 and did not find any significant association with BRAF mutation status (Table III). Two recent meta- analyses in adults found a significant association of BRAF V600E with lymphatic metastases, 8 tumor size > 1 cm, 8 and extrathyroidal extension. 7,8 One study did not examine association with lymphovascular invasion, 7 whereas one did not demonstrate an association of lymphovascular inva- sion with BRAF V600E. 8 Our findings are also in agree- ment with the existing pediatric literature, which found no association of the BRAF V600E mutation with lymphatic or distant metastases 11,14 or extrathyroidal extension. 11 We acknowledge the limitations of this study in that it is a retrospective review with a small sample size. The study is insufficiently powered to detect a statistically sig- nificant association between the BRAF mutation and aggressive disease characteristics, if one truly exists. Addi- tionally, certain variables such as tumor size, lymphovascu- lar invasion, and extrathyroidal or extracapsular extension were inconsistently reported in our pathology reports. Finally, patient follow-up information was not always avail- able, making association with recurrence unclear. CONCLUSION The BRAF V600E mutation may be more prevalent than previously thought in pediatric patients with PTC, but it is not associated with aggressive disease character- istics. This is in contrast to the findings in the adult popu- lation, where a BRAF gene mutation may be an indication for more aggressive surgical treatment. We cannot sup- port that conclusion in the pediatric population. Acknowledgments The authors acknowledge Shalene Ashby, MS, CHES, for assistance with statistical analysis.
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Givens et al.: BRAF V600E and Pediatric Thyroid Carcinoma
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