259 / 280
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
237