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Is the BRAF V600E mutation useful as a predictor of preoperative risk in papillary thyroid cancer? The American Journal of Surgery. Title:. Papillary thyroid carcinoma (PTC) is the most common malignancy arising from thyroid follicular cells. Although PTC frequently - PowerPoint PPT PresentationTRANSCRIPT
TITLE:
Is the BRAFV600E
mutation useful as apredictor of preoperative risk in papillary
thyroid cancer?
The American Journal of Surgery
INTRODUCTION:
Papillary thyroid carcinoma (PTC) is the most common malignancy
arising from thyroid follicular cells. Although PTC frequently
metastasizes to regional lymph nodes, it generally shows an indolent
character and slow growth. However, PTCs showing certain
characteristics have poor prognosis and are classified into high-risk
groups. There are several classification systems for evaluation of the
progression of thyroid carcinoma.
These systems are mainly used for the identification of
patients with a poor prognosis to ensure that they receive
additional treatment, such as radioiodine ablation and more
frequent follow-up monitoring. However, these classification
Systems include postoperative data for guidance with regard
to the extent of initial surgical resection
Moreover, many patients (80% or more) currently diagnosed
with thyroid cancer have small, localized PTC but may
receive aggressive treatment because their risk of
recurrence and mortality cannot be reliably predicted
preoperatively
By contrast, some clinicians in Japan have suggested that
patients with a solitary small (1.0 cm) PTC may require
observation only, if there is no evidence of lymph node
Metastasis or multifocal disease on neck ultrasound.Although
the death rate from thyroid cancer has not changed,
The recently discovered activating mutation in the gene for the B
type Raf kinase, BRAF, is the most common genetic alteration in
thyroid cancer.The most common activating BRAF mutation, a
thymidine-to-adenine Transversion at nucleotide 1799, resulting
in a valine to Glutamic acid substitution at amino acid 600
(V600E), has Been observed in approximately 29% to 83% of
PTCs.The prevalence of this mutation has been found to differ
According to PTC subtype.
Although several studies have reported that this mutation is
related to poor prognosis and reflects aggressive Clinicopathologic
features in patients with PTC, especially in Western countries,
other studies have found no statistically significant association
between the BRAFV600E mutation and poor prognosis and
Aggressive Clinicopathological characteristics, including frequent
lymph node metastasis in this disease, especially in eastern
countries.
To date, the UICC/AJCC TNM staging system has been the
most widely adopted classification systems for evaluation
of the prognosis of thyroid carcinoma. Therefore, we
evaluated clinicopathologic factors that were suspicious
for associationWith poor prognosis based on TNM staging
And analyzed the association between the BRAFV600E
mutation and these Clinicopathologic factors
MATERIALS AND METHODS: PATIENTS
Thyroid tumor tissues were sampled from 424 patients with PTC who
underwent various thyroidectomy from September 2008 to December
2009 at the Department of Surgery, Seoul St. Mary’s Hospital, Seoul,
Korea. We Obtained informative results for 424 patients, and these
patients were enrolled in this study. These 424 patients included 79 men
and 345 women, and the mean age of patients at surgery was 46.9 ± 12.4
(17 to 76) years.
Total or near total thyroidectomy was performed for 367 patients (86.8%),
whereas the remaining patients underwent more limited thyroidectomy, such as
subtotal (23 patients), completion (5 patients) thyroidectomy, and lobectomy
(29 patients). Central compartment dissection alone was performed For 415
patients (97.9%), and modified radical neck dissection, including central neck
dissection, was performed on 9 patients (2.1%).
RESULTSWe investigated lymph node metastasis in 424 patients
with PTC who underwent thyroidectomy and neck dissection.
Of these patients, lymph node metastasis occurred in
205 (48.3%) patients. (Table 1)
Table 2 shows the relationship between lymph
node metastasis and clinicopathological features that were
suspected to have a prognostic effect to PTC. Lymph node
metastasis did not differ significantly between patients with
and without the BRAFV600E mutation.
We then performed multivariate analysis. Table3 Shows that age
<45, size of cancer >1 cm, extrathyroidal extension, and galectin 3
expression were independently associated with lymph node
metastasis of PTC. We investigated the BRAFV600E mutation in 424
patients with papillary thyroid cancer. Of these patients, 335 (79.0%)
Patients showed the BRAFV600E mutation.
Table 4 shows the relationship between the BRAFV600E mutation and
Clinicopathologic features, including the Metastasis, Patient Age,
Completeness of resection, local Invasion and Tumor Size (MACIS)
score, which was identified as a reliable prognostic predicting
value.
The incidence of the BRAFV600E mutation was not linked to the
MACIS score, age, sex, or cancer size on univariate analysis.
Extrathyroidal extension and galectin 3 expression, multifocality,
And variant of PTC were associated with the BRAFV600E mutation.
Extrathyroidal extension is an independent factor affecting the
BRAFV600E mutation on multivariate analysis(Table 5).
The incidence of classic PTC was higher at 84.3% Than the follicular
variant of PTC at 7.6%, and, additionally, there was an oncocytic
Type and 36 (8.7%) mixed types. The prevalence of the BRAFV600E
mutation in the follicular variant of PTC was lower at 62.5%,
respectively, than that of classic PTC at 79.7%.
COMMENTS
This study shows that the BRAFV600E mutation is not associated with
a high-risk MACIS score and lymph node metastasis. However, the
BRAFV600E mutation differed Significantly between patients with and
Without extrathyroidal extension. Multivariate analysis showed that
Extrathyroidal extension is independently associated with the
BRAFV600E mutation.
These findings are not consistent with previous reports, particularly in
Western areas.However, a recent study in Japan showed that the BRAFV600E
mutation did Not show any relationship with prognostic factors, including
lymph node metastasis.In addition, other study groups in Korea have
reported that age distribution, sex ratio,extrathyroid extension,
multifocality, and lymph node metastasis did not differ significantly
between patients with and without the BRAFV600E mutation.
In our study population, age< 45 and male sex,size Of cancer ≥1 cm,
extrathyroidal extension, galectin 3 expression,and multifocality
were associated with lymph node metastasis of PTC.
multivariate analysis showed that extrathyroidal extension is
independently associated with the BRAFV600E mutation. The
Extrathyroidal extension is one of the risk factors of lymph node
metastasis in our study, and the other authors have reported it.The route
for metastasis and locoregional invasion preferentially occurs by
lymphatic vessels.In our study, the BRAFV600E Mutation is not associated
with lymphatic invasion (Table 4).
Therefore, we believe that the BRAFV600Emutation Does not affect
lymph node metastasis directly. However, the BRAFV600E mutation
may affect lymph node metastasis indirectly because it is
Associated with extrathyroidal extension independently.
The BRAFV600E mutation is the most common genetic alteration observed in
thyroid cancer and occurs in 36% to 65% of PTCs in Western countries. However,
the BRAFV600E mutation was found in 79% of patients in our study. This frequency
of the BRAFV600E mutation is higher than that of other studies. The BRAFV600E
Mutation of PTC in Korea, a country where iodine intake is very high, is
Reported to be highly prevalent (52%–87%) compared with Western
countries.This may be Because most PTCs in Korea are the classic type.
Our study cannot show the association between the prognosis of PTC and
the presence of the BRAFV600E mutation; however, we found that the
BRAFV600E mutation is not associated with a high MACIS score and lymph
node metastasis, cancer size, and sex in our study group. A long-term
follow-up study is needed to identify the association between the
prognosis of PTC and the BRAFV600E mutation.
Although there are only a few published studies of interracial and
regional differences between the BRAFV600E mutation and the
prognosis of PTC, it appears to be present in the difference between
eastern and western countries.
CONCLUSIONS
We showed that the BRAFV600E mutation is commonly found in the Korean
Population rather than in Western populations;
however, it is not related to a high-risk MACIS score and several high-risk
clinicopathologic factors, including lymph node metastasis. However, it is
Related to a few High risk clinicopathologic factors including multifocality
And extrathyroidal extension. Therefore, it is not clear that The BRAFV600E
mutation is useful for the prediction of a poor prognosis of PTC.
In addition, although the BRAFV600E Mutation may
play some role in the development of local carcinoma, it is not
appropriate for determination of the extent of surgical treatment or
postoperative treatment and planning of follow-up monitoring in
PTC according to the existence of the BRAFV600E mutation.