257 / 280
with a higher MACIS score in BRAF wild-type patients.
The presence of tumor size
>
1 cm was not statistically
associated with the BRAF V600E mutation (
P
5
.851).
Our literature review identified a total of five stud-
ies that examined pediatric patients with well-
differentiated thyroid cancer and assessed for the BRAF
gene mutation. Prevalence was variable ranging from
0% to 36%. Two studies reviewed the disease character-
istics of the patients and did not find an association
between BRAF V600E and aggressive disease. When
the results of our study were added to the existing
literature, the cumulative presence of BRAF V600E in
pediatric thyroid cancer was 28.4% (Table III).
DISCUSSION
The BRAF V600E gene mutation has been increas-
ingly studied in various disease entities such as thyroid
carcinoma, melanoma, astrocytoma, and colon cancers.
Chemotherapeutic agents have been successfully used to
target this gene mutation in clinical trials in adults.
Numerous studies have attempted to correlate the
TABLE I.
Patient Characteristics.
Patient
No.
Age,
yr
Tumor
Size, cm
Lateral
Neck
Disease
Central
Neck
Disease
Pulmonary
Metastases Recurrence
Histology
Lymphovascular
Invasion
Extracapsular
Extension
MACIS
Score
BRAF
Mutation
1
15.2 1.9
N
N
N
NR
PTC
NR
N
3.67 Positive
2
11.2 6
Y
Y
Y
NR
PTC
Y
Y
8.9 Negative
3
10.9 NR
Y
Y
N
Y
FVPTC
Y
Y
— Negative
4
13.4 3
Y
Y
Y
NR
FVPTC
NR
NR
8 Negative
5
13.7 0.3
Y
Y
N
N
FVPTC
Y
Y
4.19 Negative
6
2.8 2.6
N
Y
Y
N
FVPTC
Y
NR
7.88 Negative
7
12.4 1.3
N
N
N
N
PTC
N
Y
3.49 Positive
8
11.8 3.3
N
N
N
N
FVPTC
NR
NR
4.09 Negative
9
16.2 0.3
N
N
N
NR
PTC
N
N
3.19 Negative
10
13.8 2.7
Y
Y
N
Y
PTC
Y
Y
4.91 Positive
11
18.3 NR
Y
Y
N
N
PTC
NR
NR
— Positive
12
12.5 3.9
Y
Y
Y
NR
FVPTC
Y
Y
8.27 Negative
13
12.8 1.4
N
N
N
N
FVPTC
N
N
3.52 Negative
14
15.1 0.8
N
N
N
N
PTC
N
N
3.34 Positive
15
13 1.6
N
Y
N
N
PTC
Y
NR
4.58 Positive
16
16.7 2.3
N
Y
Y
N
PTC,
oncocytic variant
Y
Y
4.79 Negative
17
15.5 4.2
N
Y
N
N
PTC
Y
Y
5.36 Positive
18
14.8 0.5
Y
Y
N
N
PTC–TCM
Y
N
4.25 Negative
19
17.4 0.9
N
Y
N
N
PTC
NR
NR
4.37 Negative
FVPTC
5
follicular variant of papillary thyroid carcinoma; MACIS
5
metastases, age at diagnosis, completeness of resection, invasion, size of the tumor
scoring; N
5
no; NR
5
not reported; PTC
5
papillary thyroid carcinoma; TCM
5
tall cell morphology; Y
5
yes.
TABLE II.
Association of BRAF V600E With Disease Factors.
Independent Variable
Wild-Type BRAF
Mutant BRAF
Significance
Percentage with PTC histology
33.3% (4/12)
100% (7/7)
P
5
.013
Percentage with lateral neck metastases
50% (6/12)
28.5% (2/7)
P
5
.633
Percentage with central neck metastases
75% (9/12)
57.1% (4/7)
P
5
.617
Percentage with pulmonary metastases
42% (5/12)
0% (0/7)
P
5
.106
Percentage with lymphovascular invasion
77.8% (7/9)
60% (3/5)
P
5
.580
Percentage with extrathyroidal extension
62.5% (5/8)
60% (3/5)
P
5
1.00
Percentage with microcarcinoma
36.3% (4/11)
16.7% (1/6)
P
5
.851
Average age, yr*
12.9
14.8
t
52
1.221,
P
5
.239
Average MACIS score*
5.59
4.23
P
5
.087
Average tumor size, cm*
2.23
2.08
t
5
0.176,
P
5
.863
*These continuous variables describe differences between the two groups BRAF V600E and BRAF wild-type.
MACIS
5
metastases, age at diagnosis, completeness of resection, invasion, size of the tumor; PTC
5
papillary thyroid carcinoma.
Laryngoscope 124: September 2014
Givens
et
al.: BRAF
V600E
and
Pediatric
Thyroid Carcinoma
235