vol 7, no 3 (2018): (in press for december 2018)
TRANSCRIPT
Vol 7, No 3 (2018): (In Press For December 2018) Table of Contents
ORIGINAL ARTICLE
Urban Space Preferences among Older Adults from a Sociodemographic Perspective
Bahare Fallahi, Yadollah Abolfathi Momtaz
Online First: June 15, 2018
| DOI: 10.15562/bmj.v7i3.1183
Abstract
ORIGINAL ARTICLE
Characterization and Identification of Poliovirus from the Environment in Indonesia 2015
Bambang Heriyanto, Nike Susanti, Vivi Setiawaty
Online First: June 23, 2018
| DOI: 10.15562/bmj.v7i3.963
Abstract
ORIGINAL ARTICLE
The alterations of XRCC1 gene’s polymorphism with a different SNP is involved in breast
cancer
Varesh Shams Akhzari, Fatemeh Asgharpour–Dil, Mohsen Shoja, Fatemeh Dehbandi,
Shahrbano Keyhaniyan, Roya Khaksar, Seyedeh Elham Norollahi, Abbas Ghayoumi Javinani,
Sahar Ghazanfari, Ali Akbar Samadani
Online First: June 25, 2018
| DOI: 10.15562/bmj.v7i3.942
Abstract
ORIGINAL ARTICLE
The relationship between anterior tooth loss and quality of life among elderly in Posbindu,
Bojongnangka, Kelapa Dua Sub-District, Tangerang, Jakarta-Indonesia
Helwiah Umniyati, Audiawati Surachmin, Ghea Ambarsati
Online First: June 28, 2018
| DOI: 10.15562/bmj.v7i3.1192
Abstract
ORIGINAL ARTICLE
Effect of corticosteroid and vitamin D3 as combined therapy on 25 (OH) vitamin D serum
level and regulatory T (TReg) cells population in children with idiopathic nephrotic
syndrome
Krisni Subandiyah, Harinda Khanifa, Astrid Kristina Kardani
Online First: June 28, 2018
| DOI: 10.15562/bmj.v7i3.769
Abstract
ORIGINAL ARTICLE
A comparative assessment of alveolar bone loss using bitewing, periapical, and panoramic
radiography
Cek Dara Manja, M. Edwin Fransiari
Online First: July 01, 2018
| DOI: 10.15562/bmj.v%vi%i.1191
Abstract
ORIGINAL ARTICLE
Nutrition Status affects High School Students achievement in: A massive prospective
cohort study at Sleman, Yogyakarta Indonesia
Zefanya Ricky Wedu, Eti Poncorini Pamungkasari, Sapja Anantanyu
Online First: July 04, 2018
| DOI: 10.15562/bmj.v7i3.973
Abstract
ORIGINAL ARTICLE
Effect of aspirin desensitization on nasal polyps recurrence and remission based on
imaging studies in patients with triple symptoms of asthma, aspirin sensitivity, and nasal
polyps and the impact of this method on their quality of life
Seyyed Mostafa Hashemi, Seyyed Mojtaba Abtahi, Parisa Damirchi
Online First: July 04, 2018
| DOI: 10.15562/bmj.v7i3.896
Abstract
ORIGINAL ARTICLE
Mini Health Technology Assessment of Urban and Rural Health Care in Indonesia
Ferdy Iskandar, Fabianto Santoso, Angela Franzeska, Yenna Tasia, Kamajaya Mulyana
Online First: July 04, 2018
| DOI: 10.15562/bmj.v7i3.932
Abstract
ORIGINAL ARTICLE
BRAF V600E expression found in aggressive papillary thyroid carcinoma (PTC), lymph
node metastasis, and extra-thyroid extension
Made Priska Rusmana, Ni Putu Sriwidyani, I Gusti Ayu Sri Mahendra Dewi
Online First: July 04, 2018
| DOI: 10.15562/bmj.v7i3.1201
Abstract
ORIGINAL ARTICLE
Medical pedagogical approach to the development of health-saving environment in
educational establishments
Akishina Ekaterina Mikhailovna, Marina Stanislavovna Krasilnikova
Online First: July 13, 2018
| DOI: 10.15562/bmj.v7i3.1089
Abstract
ORIGINAL ARTICLE
Mean Platelet Volume (MPV) as an inflammatory marker in type 2 diabetes mellitus and
obesity
Gulali Aktas, Mehmet Zahid Kocak, Tuba Taslamacioglu Duman, Edip Erkus, Burcin Meryem
Atak, Mustafa Sit, Haluk Savli
Online First: July 17, 2018
| DOI: 10.15562/bmj.v7i3.806
Abstract
ORIGINAL ARTICLE
Investigating the effects of nurse post-discharge follow-up phone calls on the self-efficacy of
patients suffering from stroke
Hamid Taghinejad, Masoumeh Otaghi, Azam Nikan, Reza Beiranvand
Online First: July 19, 2018
| DOI: 10.15562/bmj.v7i3.1008
Abstract
ORIGINAL ARTICLE
Comparison of insulin therapy outcomes (satisfaction with treatment, pain during
injection, follow-up) in patients using insulin pen and insulin infusion with syringe
Sanaz Azami, Mosayyeb Mozafari, Hassan Pourabdollah
Online First: July 19, 2018
| DOI: 10.15562/bmj.v7i3.1009
Abstract
ORIGINAL ARTICLE
The effect of probiotic Lactobacillus casei supplementation on the secretory
immunoglobulin A level in the saliva of wistar rats
Maulida Hayati, Herry Herman, Andri Rezano
Online First: July 21, 2018
| DOI: 10.15562/bmj.v7i3.1171
Abstract
ORIGINAL ARTICLE
The effectiveness of red betel leaf (Piper crocatum) extract against periodontal pathogens
Herryawan Herryawan, Indah Puti Rahmayani Sabirin
Online First: July 21, 2018
| DOI: 10.15562/bmj.v7i3.1173
Abstract
ORIGINAL ARTICLE
Accuracy of cerebrospinal fluid and serum S100B protein in the diagnosis of bacterial
meningitis in children
Dewi Sutriani Mahalini, Anak Agung Raka Sudewi, Soetjiningsih Soetjiningsih, I Gde Raka
Widiana
Online First: July 21, 2018
| DOI: 10.15562/bmj.v7i3.1202
Abstract
REVIEW
Current clinical status of hydrotherapy; an evidence based retrospective six-years (2012-
2017) systemic review
Sameera Mohammed Almassmoum, Eman Ahmed Balahmar, Shoroug Taye Almutairi, Goot
Albuainain, Rizwan Ahmad, Atta Abbas Naqvi
Online First: June 21, 2018
| DOI: 10.15562/bmj.v7i3.1159
Abstract
CASE REPORT
Breast tuberculosis in Jakarta: Review of 7 cases
Farida Briani Sobri, Odetta Natatilova Halim
Online First: June 17, 2018
| DOI: 10.15562/bmj.v7i3.1081
Abstract
Editor-in-Chief
Prof. Dr. Sri Maliawan, SpBS (Scopus ID= 15738530400, h-index= 5, [email protected] / [email protected])
Department of Neuro Surgery, Udayana University
Sanglah General Hospital
Bali - Indonesia
Associate Editor
Prof. Putra Manuaba, M.Phil (Scopus ID= 8412278400, h-index= 3, [email protected]
Biomedicine Postgraduate Program, Udayana University
Bali - Indonesia
Prof. Ketut Suwiyoga, SpOG ([email protected])
Faculty of Medicine, Udayana University, Sanglah Hospital Denpasar, Bali-Indonesia
Editorial Board for Regional America
Ankit Sakhuja, M.B.B.S., F.A.C.P., F.A.S.N. (Scopus ID= 16744977200, h-index= 8, [email protected])
Nephrology and Hypertension Cleveland Clinic (United States)
Editorial Board for Regional Australia
Prof. John Svigos, MB. BS. DRCOG., FRCOG., RANZCOG (Scopus ID= 6603773825, h-index= 7 ,[email protected])
Ashford Hospital & Faculty of Health Sciences, University of Adelaide, Australia
dr Deasy Ayuningtyas Tandio MPH-MBA. Email: [email protected]
James Cook University Australia Master of Public Health Master Of Business Administration,
Indonesia
(orcidID: 0000-0001-7847-2831, H-index = 1).
Editorial Board for Regional Europa
Prof. Harald Hoekstra (Scopus ID= 36038081900, h-index= 53 ,[email protected])
Universitair Medisch Centrum Groningen, Division of Surgical Oncology, Groningen the
Netherland
Editorial Board for Regional Asia
Prof Huang Qin (Scopus ID= 8570628900, h-index= 1, [email protected])
Chairman Dept. of Neurosurgery, Guangdong 999 Hospital Guangzhou China
Prof. Soo Khee Chee (Scopus ID= 7005885770, h-index= 8, [email protected])
SGH (Singapore General Hospital), National University Hospital, Duke Medical Center
Singapore
Dr. G Sai sailesh Kumar, Ph.D (Scopus ID= 56176035300, h-index= 5, [email protected])
Department of Physiology, Little Flower Institute of Medical Sciences and Research, Angamaly,
Kerala,India
Assoc. Prof. Mohammad Amin Bahrami (Scopus ID= 55524082200, [email protected])
Head of healthcare management department, Shahid Sadoughi University of Medical Sciences,
Yazd,Iran
Dr. Tanveer Beg, PhD (Scopus ID: 6505772852; h-index = 11; [email protected])
Assistant Professor, Department of Biology, Faculty of Science, Jazan University, Jazan, Saudi
Arabia.
Editorial Board Members
Prof. Andi Asadul Islam ([email protected])
Faculty of Medicine Hasanudin University, Makasar-Indonesia
Prof. Dr. dr. Abdul Hafid Bajamal, Sp.BS ([email protected])
Faculty of Medicine Airlangga University, Surabaya-Indonesia
dr. I.B. Amertha P. Manuaba, SKed, MBiomed. ([email protected] / [email protected])
(ResearcherID: P-9169-2016) (orcid.org/0000-0001-6647-9497)
Scopus ID=57195520004
Biomedicine Magister Program, Udayana University, Indonesia
Editorial inquiries to be addressed to: [email protected]
-------------------------------------------------------------------------------- Reviewer
Prof. Dr. dr. Raka Sudewi, SpS (K) ([email protected]/[email protected])
Universitas Udayana, Department of Neurology, Bali, Indonesia
Scopus Author ID: 12140226200 (H-indexs: 6)
Dr. dr. Tjok Gd. Bgs. Mahadewa, S.Ked, Sp.BS(K)-Spine ([email protected] )
Universitas Udayana, Department of Neurosurgery, Bali, Indonesia
Scopus Author ID: 6507494320 (H-indexs: 3)
dr. Dewa Putu Wisnu Wardhana, MD, FICS
Universitas Udayana, Department of Neurosurgery, Bali, Indonesia
Prof. Dr. dr. Made Wardhana, SpKK(K), FINSDV, FAADV ([email protected])
Universitas Udayana, Department of Dermatology and Venerology, Bali, Indonesia
Dr. dr. A A Mas Putrawati Triningrat, Sp. M (K) ([email protected])
Universitas Udayana, Department of Opthalmology, Bali, Indonesia
Dr.dr.Tjokorda Gde Agung Senapathi,SpAn.KAR ([email protected])
Universitas Udayana, Department Anesthesia & Reanimation, Bali, Indonesia
Scopus Author ID: 36519653900 (H-indexs: 2)
ORIGINAL ARTICLEBali Medical Journal (Bali Med J) 2018, Volume 7, Number 3: 658-662P-ISSN.2089-1180, E-ISSN.2302-2914
658 Open access: www.balimedicaljournal.org and ojs.unud.ac.id/index.php/bmj
CrossMarkPublished by DiscoverSys
ABSTRACT
Purpose: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Most PTC patients have a good prognosis. However, about 10% cases showed aggressive behavior. Its association with BRAF V600E mutation is still controversy. The purpose of this study is to prove the association between BRAF V600E expression and PTC aggressiveness.Material and methods: This cross-sectional analytic study involving 36 PTC patients. Tumor aggressiveness was determined based on at least one of these categories: tumor size, lymph node metastasis, extra-thyroid extension and vascular invasion. Immunohistochemistry staining VE1 was performed to assess BRAF V600E expression. Chi-square test was used to assess
the association between BRAF V600E expression and tumor aggressiveness.Results: BRAF V600E expression was found in 58.3% of cases of aggressive PTC group. There was a significant difference between BRAF V600E expression in aggressive and non-aggressive PTC group (p = 0.021). There was a significant association between BRAF V600E expression and lymph node metastasis (p = 0.005) and extra-thyroid extension (p = 0.011), but no significant association between BRAF V600E expression and tumor size (p = 0.252) and vascular invasion (p= 0.367).Conclusion: BRAF V600E expression has an association with tumor aggressiveness in PTC, as well as with lymph node metastasis and extra-thyroid extension.
Keywords: BRAF, V600E, aggressiveness, papillary thyroid carcinoma.Cite This Article: Rusmana, M.P., Sriwidyani, N.P., Dewi, I.G.A.S.M. 2018. BRAF V600E expression found in aggressive papillary thyroid carcinoma (PTC), lymph node metastasis, and extra-thyroid extension. Bali Medical Journal 7(3): 658-662. DOI:10.15562/bmj.v7i3.1201
BRAF V600E expression found in aggressive papillary thyroid carcinoma (PTC), lymph node
metastasis, and extra-thyroid extension
Made Priska Rusmana,1 Ni Putu Sriwidyani,2* I Gusti Ayu Sri Mahendra Dewi3
INTRODUCTION
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and tends to have indo-lent biological behavior and with good prognosis.1 However, about 5-10% of cases recurred.2 Some clinicopathological features are considered as a poor risk factor: large tumor size, extra-thyroid extension, lymph node and distant metastasis and higher stage.3 Aggressive clinicopathological features were related to some genetic changes in PTC, the most frequently observed is BRAF muta-tion that found in 29-83% of cases.4 BRAF muta-tion induces Mitogen-Activated Protein Kinase (MAPK) pathway that plays an important role in tumorigenesis.5 About 90% BRAF mutation in thyroid carcinoma is thymine to adenine transver-sion that results in valine (V) to glutamic acid (E) substitution in amino acid 600 (V600E).
Various systems have been established to assess thyroid carcinoma prognosis. American Thyroid Association (ATA) risk stratification system uses tumor size, nodal metastasis, extra-thyroid exten-sion, vascular invasion and BRAF V600E mutation as criteria of prognosis in differentiated thyroid carcinoma.6 Previous study about the associa-tion between BRAF V600E mutation with some
aggressive clinicopathological parameters in PTC showed inconsistent results. The aim of this study was to determine the association between BRAF V600E expression and tumor aggressiveness in PTC.
MATERIAL AND METHODS
This study was a cross sectional analytic study of 36 PTC patients at Sanglah Hospital from 1 January until 31 December 2017. Diagnosis of PTC was from microscopic evaluation based on a set of distinctive nuclear features: (1) changes in size and shape, (2) irregularities of the membrane, and (3) chromatin characteristics.1 All PTC variants based on the WHO classification 2017 were included.
Tumor aggressiveness evaluationTumor aggressiveness of PTC determined by at
least fulfill one of following categories: tumor size, lymph node metastasis, extra-thyroid extension and vascular invasion. The evaluation was from clinical, macroscopic, and/or microscopic data through histopathologic examination using Hematoxylin-Eosin staining. Tumor size >4 cm was considered aggressive tumor.1, 7 Lymph node metastasis was determined based on clinical, radiological, and/or microscopic data. Metastasis was considered posi-tive if malignant cells were present in at least one
1Resident of Anatomic Pathology Department, Faculty of Medicine, Udayana University, Sanglah Hospital, Denpasar, Bali, Indonesia; 2, 3Lecturer of Anatomic Pathology Department, Faculty of Medicine, Udayana University, Sanglah Hospital, Denpasar, Bali, Indonesia
*Correspondence to: Ni Putu Sriwidyani, Lecturer of Anatomic Pathology Department, Faculty of Medicine, Udayana University, Sanglah Hospital, Denpasar, Bali, Indonesia [email protected]
Received: 2018-05-25 Accepted: 2018-6-28 Published: 2018-9-1
Volume No.: 7
Issue: 3
First page No.: 658
P-ISSN.2089-1180
E-ISSN.2302-2914
Doi: http://dx.doi.org/10.15562/bmj.v7i3.1201
ORIGINAL ARTICLE
659Published by DiscoverSys | Bali Med J 2018; 7(3): 658-662 | doi: 10.15562/bmj.v7i3.1201
ORIGINAL ARTICLE
regional lymph node.6 The extra-thyroid extension was tumor extends beyond the thyroid capsule and invades any of the following: muscle, subcutaneous soft tissue, larynx, trachea, esophagus, recurrent laryngeal nerve, prevertebral fascia, mediastinal vessel, or encase carotid artery.1 Vascular invasion was tumor cell invasion into the blood vessel within or beyond tumor capsule, or within organ capsule in the un-encapsulated tumor. Intravascular tumor cells should be attached to blood vessel walls, covered endothelial cells or in thrombus / fibrin.1, 6
BRAF immunostaining and interpretationThe selected paraffin blocks were sliced into 4 mm thickness for immunostaining. Staining using Ventana BenchMark XT immunostainer with primary antibody mouse anti-human BRAF V600E (VE1, Spring Bioscience, USA) was performed.
Tumor cell with BRAF V600E expression showed cytoplasmic staining. BRAF V600E expression was determined using a semi-quantitative method by calculating the percentage of positive tumor cells and its intensity. The intensity was categorized into strong (+3), moderate (+2), weak (+1), and absent (0).8 Strong intensity if the immune-reactivity
Table 1 BRAF V600E expression and tumor aggressiveness in PTC
Characteristics
BRAF V600E
Positive (n = 21; 58.3% ) Negative (n = 15; 41.7%)
Tumor size≤ 4 cm 27 75.0> 4 cm 9 25.0
Lymph node metastasisPositive 9 25.0Negative 27 75.0
Extra-thyroid extensionPositive 8 22.2Negative 28 77.8
Vascular invasionPositive 6 16.7Negative 30 83.3
Table 2 Association between BRAF V600E expression and tumor aggressiveness of PTC
Aggressiveness of PTC
OR 95% CI pAggressive
n (%)Non Aggressive
n (%)
BRAF V600E Expression Positive 12 (57.1) 9 (42.9) 8.67 1.55 to 48.47 0.021Negative 2 (13.3) 13 (86.7)
Total 14 (38.9) 22 (61.1)
Figure 1 BRAF V600E expression was evaluated by measuring staining intensity and percentage of tumor cells. (A) Absent (0), (B) weak (+1) intensity, (C) moderate (+2) intensity, and (D) strong (+3) intensity
660 Published by DiscoverSys | Bali Med J 2018; 7(3): 658-662 | doi: 10.15562/bmj.v7i3.1201
ORIGINAL ARTICLE
of tumor cell was stronger or the same as colloid staining, diffuse and clearly seen at 40 times magni-fication. Moderate intensity if tumor cell showed clear cytoplasmic staining but weaker than colloid staining and easily seen at 100 times magnifica-tion. Weak intensity if tumor cell showed vaguely staining or difficult to recognize. Absent if all of the tumor cells were not stained.8, 9 Percentage of tumor cells was assessed in the range of 0% to 100%. BRAF V600E expression was positive if > 10% of tumor cells showed positive staining with moderate or strong intensity.9
Statistical analysisThe association between BRAF V600E expression and tumor aggressiveness was determined by Chi-square test with p < 0.05 significance, using SPSS 20.0 software. Association between BRAF V600E and each clinicopathological characteristic was tested with Fisher exact test.
RESULTS
The mean age of patients was a 50.03 ± 12.81 year (range 23-75 year). Women were more frequent than men [11 (30.6%) were men, and 25 (69.4%) were women]. Six PTC variants were identified: 16 (44.4%) cases classic variant, 9 (25.0%) cases follic-ular variant, 6 (16.7%) cases papillary microcarci-noma variant, 2 (5.6%) cases oncocytic variant, 1 (2.8%) case solid/trabecular variant, and 2 (5.6%) cases tall cell variant. Multifocal PTC was found in 14 (38.9%) cases. Patient distribution based on aggressive clinicopathological parameters was described in table 1.
From 36 patients, 38.9% cases were aggressive, and 61.1% of cases were non-aggressive. BRAF V600E immunostaining showed 21 (58.3%) cases were positive and 15 (41.7%) cases were negative. Chi-square analysis showed a significant difference between BRAF V600E expression in an aggressive and non-aggressive group of PTC (p = 0.021). (Table 2) Fisher Exact test showed no significant difference between BRAF V600E expression in tumor size >4 cm and tumor size ≤ 4 cm (p = 0.252), significant difference of BRAF V600E expression in PTC with and without lymph nodes metastasis (p = 0.005), significant difference of BRAF V600E expression in PTC with and without extra-thyroid extension (p = 0.011), no significant difference in BRAF V600E expression in PTC with and without vascu-lar invasion (p = 0.367). Patient with positive BRAF V600E expression had 8.67 times higher risk of becoming an aggressive PTC compared with a patient with negative BRAF V600E expression.
DISCUSSION
BRAF V600E mutation is the most common RAF mutation that found in PTC. This mutation has also been widely studied in malignant melanoma, colon, and ovarian cancer. This mutation cause transverse of Thymine into Adenine in exon 15 in nucleotide 1799 (T1799A), which resulted in the substitution of valine to glutamic acid at 600 positions.10 BRAF V600E mutation is associated with aggressive clin-icopathological features.11 The standard method for BRAF mutation identification is DNA-based molecular examination, but it is expensive and time-consuming.8 Currently, immunohistochemis-try V600E (VE1) antibody to identify BRAF V600E mutation has been developed. This method has good accuracy (sensitivity and specificity of 98% to 100%), with shorter time and lower cost.12, 13
The prevalence of BRAF V600E mutation on PTC showed varying numbers in different coun-tries. A meta-analysis study by Li et al. (2012) in the United States revealed a prevalence rate of 50.9%.2 Some studies in China reported a prevalence rate of 30-80%, while in Japan and North Korea the prevalence rate was 60-90%.14 Papillary thyroid carcinoma mostly occurs at the age of 31-49 years, with a male to female ratio of 1 : 4.1 More than half of the patients in this study showed BRAF V600E mutation, with mean age was 50.03 year, and PTC with aggressive behavior showed a slightly higher age. Female was twice than men. The results of this study were similar with the study of Lim et al. (2017) in the United States that showed the domi-nant patients were female (75%) with a mean age 48 years.15 The study by Abd Elmageed et al. (2016) in the United States in 130 patients with PTC, the mean age of the patients was 49.3 year, and 73% of the cases were female.12
Different aggressiveness parameters have been reported in various studies of PTC. Currently, the BRAF V600E mutation has been known to be used as an additional prognostic factor in PTC. ATA Modified Initial Risk Stratification System 2015 guideline recommendation was used as the basis for this study. The guidelines described the impor-tance of the correlation between BRAF V600E mutation and other prognostic factors, i.e., tumor size, lymph nodes metastasis, extra-thyroid exten-sion, and vascular invasion.6, 16 Additional of BRAF V600E mutation status can improve the accuracy of prediction related to recurrence risk. This study used at least one of these four categories to deter-mine the aggressiveness of PTC.
Positive BRAF V600E expression was found more frequent in aggressive PTC group. This study
661Published by DiscoverSys | Bali Med J 2018; 7(3): 658-662 | doi: 10.15562/bmj.v7i3.1201
ORIGINAL ARTICLE
showed that patient with positive BRAF V600E expression had 8.67 times higher risk of becom-ing an aggressive PTC compared with a patient with negative BRAF V600E expression. Aggressive PTC will affect the prognosis of the patient with decreased survival rate. It has been reported that in aggressive PTC, especially in stage IV, survival rate decline to 41%. Aggressive PTC primarily with lymph nodes metastasis and extra-thyroid extension were also reported to be associated with an increased risk of recurrence. Overall recurrence rates were reported at 15-35%.1 The addition of BRAF V600E mutation in correlation with the four categories aggressiveness of PTC will increase the prediction value of recurrence. Tumor recurrence will require advanced therapy, such as re-surgery and additional radioiodine therapy that affect the quality of life of the patient. The high recurrence rate in aggressive PTC patients with BRAF V600E mutation has been reported in several studies. A meta-analysis study by Chen et al. and Liu et al. (2016) showed PTC patients with BRAF V600E mutation had an increased risk of recurrence.17
This study found that there was a tendency of BRAF V600E expression in PTC with tumor size > 4 cm, although statistically not significant. Previous studies showed inconsistent results.18,19,20,22 It seems that tumor size is not an independent factor in the prognosis of PTC.
All patients with lymph nodes metastasis in this study showed BRAF V600E expression. Similar results also reported by Na et al. (2015) in South Korea where there was a significant association between the BRAF V600E mutation and lymph nodes metastasis.8 Lymph nodes metastasis is an important risk factor for recurrence and overall survival. The criteria used by ATA Modified Initial Risk Stratification System 2015 distinguish the risk of recurrence of lymph node metastasis by the size of the node, number of positive lymph node, and extra-nodal extension.
This study showed that all patient with extra-thy-roid extension had positive BRAF V600E expres-sion. This was supported by Fraser et al. (2016) that found a significant association between BRAF V600E mutations and extra-thyroid extension.19 Meta-analysis study by Chen et al. (2016) reported that PTC with extra-thyroid extension had higher rate BRAF V600E mutation.17 The extra-thyroid extension is an aggressive feature of PTC that asso-ciated with an increased risk of recurrence. In such cases, radical surgical treatment is required.
Although there was no significant association between BRAF mutation and vascular invasion, there was a tendency of BRAF V600E expression on PTC with vascular invasion. Several studies showed
inconsistent results.2,8,20,22,23 Vascular invasion is likely not an independent risk factor for aggressive PTC.
CONCLUSION
There is an association between BRAF V600E expression and the aggressiveness of PTC, as well as lymph nodes metastasis and extra-thyroid extension. Molecular testing of BRAF mutation in thyroid carcinoma management should be done in conjunction with classical clinicopathological evaluation. A longitudinal study is needed to deter-mine the role of BRAF V600E expression in PTC prognosis.
DISCLOSURE
The authors report no conflicts of interest in this work.
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This work is licensed under a Creative Commons Attribution
BRAF V600E expression found inaggressive papillary thyroid
carcinoma (PTC), lymph nodemetastasis, and extra-thyroid
extensionby I Gusti Ayu Sri Mahendra Dewi
Submission date: 19-Mar-2019 09:17AM (UTC+0700)Submission ID: 1095714856File name: Sim_BRAF_V600E_expression_f ound_in_aggressive.pdf (667.05K)Word count: 3491Character count: 19173
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