갑상선 유두암에서 BRAFV600E 돌연변이와 연관된 임상병리학적 인자 및 초음파 소견과의 연관성

최향숙,김광민,박준범,배금석,강성준 대한갑상선-내분비외과학회 2012 The Koreran journal of Endocrine Surgery Vol.12 No.1

Purpose: This study evaluated the association of the BRAFV600E mutation with known prognostic factors and ultrasonographic characteristics in cases of papillary thyroid carcinoma. Methods: Subjects included 169 patients who received thyroidectomy at Wonju Christian Hospital under the diagnosis of papillary thyroid cancer from February 2010 to October 2011. Results: Of the total patients who received thyroidectomy, there were 128 cases (75,7%) of BRAFV600E mutation. Neither age nor sex were associated with the BRAFV600E mutation. Tumor size, shape, margin, extrathyroidal extension, central node metastasis and lateral node metastasis were found not to be associated with the BRAFV600E mutation. Tumor calcification, echogenicity and vascularity were also not associated with the mutation. Conclusion: As debate remains about the association between the BRAFV600E mutation and clincopathologic factors and ultrasonographic characteristics in cases of papillary thyroid carcinoma, further study is needed. Purpose: This study evaluated the association of the BRAFV600E mutation with known prognostic factors and ultrasonographic characteristics in cases of papillary thyroid carcinoma. Methods: Subjects included 169 patients who received thyroidectomy at Wonju Christian Hospital under the diagnosis of papillary thyroid cancer from February 2010 to October 2011. Results: Of the total patients who received thyroidectomy, there were 128 cases (75,7%) of BRAFV600E mutation. Neither age nor sex were associated with the BRAFV600E mutation. Tumor size, shape, margin, extrathyroidal extension, central node metastasis and lateral node metastasis were found not to be associated with the BRAFV600E mutation. Tumor calcification, echogenicity and vascularity were also not associated with the mutation. Conclusion: As debate remains about the association between the BRAFV600E mutation and clincopathologic factors and ultrasonographic characteristics in cases of papillary thyroid carcinoma, further study is needed.

Evaluation of Pyrosequencing Method for a BRAFV600E Mutation Test

( Seo Young Oh ),( Hoon Taek Lee ) 대한임상검사과학회 2015 대한임상검사과학회지(KJCLS) Vol.47 No.1

A fine needle aspiration biopsy (FNAB) is the primary means of distinguishing benign from malignant in thyroid nodules. However, between 10 and 30% of the FNABs of thyroid nodules are diagnosed as ``indeterminate``. A molecular method is needed to reduce unnecessary surgery in this group. In Korea, most thyroid cancer is classic papillary type and BRAFV600E mutation is highly prevalent. Thus, this study compared the pyrosequencing method with the conventional direct DNA sequencing and PCR-RFLP analysis and investigated the evaluation of preoperative BRAFV600E mutation analysis as an adjunct diagnostic method with routine FNABs. Sixty-five (78.3%) of 83 histopathologically diagnosed malignant nodule revealed positive BRAFV600E mutation on pyrosequencing analysis. In detail, 65 (83.8%) of 78 papillary thyroid carcinomas sample showed positive BRAFV600E mutation. None of 29 benign nodules had in pyrodequencing, direct DNA sequencing and PCR-RFLP. Out of 31 thyroid nodules classified as ``indeterminate`` on cytological examination preoperatively, 28 cases turned out to be malignant: 24 papillary thyroid carcinomas. Among that, 16 (66.7%) classic papillary thyroid carcinomas had BRAFV600E mutation. Among 65 papillary thyroid carcinomas with positive BRAFV600E mutation detected by pyrosequencing analysis, each 3 cases and 5 cases did not show BRAFV600E mutation by direct DNA sequencing and PCR-RFLP analysis. Therefore, pyrosequencing was superior to direct DNA sequencing and PCR-RFLP in detecting the BRAFV600E mutation of thyroid nodules (p =0.027). Detecting BRAFV600E mutation by pyrosequencing was more sensitivity, faster than direct DNA sequencing or PCR-RFLP.

The Frequency and Clinical Implications of the BRAFV600E Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades

홍아람,임정아,김태현,최훈성,유원상,민혜숙,원재경,이규은,정경천,박도준,박영주 대한내분비학회 2014 Endocrinology and metabolism Vol.29 No.4

Background: Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAFV600E, which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAFV600E mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed. Methods: The present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAFV600E mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA. Results: The prevalence of the BRAFV600E mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAFV600E mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAFV600E mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAFV600E mutation status. Conclusion: The BRAFV600E mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAFV600E-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAFV600E mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.

Evaluation of Pyrosequencing Method for a BRAFV600E Mutation Test

Oh, Seo Young,Lee, Hoon Taek 대한임상검사과학회 2015 대한임상검사과학회지(KJCLS) Vol.47 No.1

A fine needle aspiration biopsy (FNAB) is the primary means of distinguishing benign from malignant in thyroid nodules. However, between 10 and 30% of the FNABs of thyroid nodules are diagnosed as 'indeterminate'. A molecular method is needed to reduce unnecessary surgery in this group. In Korea, most thyroid cancer is classic papillary type and BRAFV600E mutation is highly prevalent. Thus, this study compared the pyrosequencing method with the conventional direct DNA sequencing and PCR-RFLP analysis and investigated the evaluation of preoperative BRAFV600E mutation analysis as an adjunct diagnostic method with routine FNABs. Sixty-five (78.3%) of 83 histopathologically diagnosed malignant nodule revealed positive BRAFV600E mutation on pyrosequencing analysis. In detail, 65 (83.8%) of 78 papillary thyroid carcinomas sample showed positive BRAFV600E mutation. None of 29 benign nodules had in pyrodequencing, direct DNA sequencing and PCR-RFLP. Out of 31 thyroid nodules classified as 'indeterminate' on cytological examination preoperatively, 28 cases turned out to be malignant: 24 papillary thyroid carcinomas. Among that, 16 (66.7%) classic papillary thyroid carcinomas had BRAFV600E mutation. Among 65 papillary thyroid carcinomas with positive BRAFV600E mutation detected by pyrosequencing analysis, each 3 cases and 5 cases did not show BRAFV600E mutation by direct DNA sequencing and PCR-RFLP analysis. Therefore, pyrosequencing was superior to direct DNA sequencing and PCR-RFLP in detecting the BRAFV600E mutation of thyroid nodules (p =0.027). Detecting BRAFV600E mutation by pyrosequencing was more sensitivity, faster than direct DNA sequencing or PCR-RFLP.

Diagnostic value of BRAFV600E mutation analysis in fine needle aspiration for evaluation of thyroid nodules

최영식,이혜원,옥소영,김부경,권수경,김정훈,정상봉 고신대학교(의대) 고신대학교 의과대학 학술지 2018 고신대학교 의과대학 학술지 Vol.33 No.1

Objectives: Ultrasound-guided fine-needle aspiration (FNA) is routinely used in the evaluation of thyroid nodules. However, it has several pitfalls, as has been noted in nondiagnostic and indeterminate cases. This study aims to investigate the value of BRAFV600E mutation co-testing in FNA cytology. Method: A total of 310 patients underwent BRAFV600E mutation co-testing in FNA cytology on thyroid nodules between June 2013 and June 2014. Of the 310 patients, 69 patients who had undergone a surgery for thyroid nodules were included in this study. The presence of the BRAFV600E mutation was determined by allele-specific polymerase chain reaction amplification of exon 15 of the BRAF gene. Results: Of 69 cases, 33 (47.8%) were BRAFV600E mutation positive. The BRAFV600E mutation was not significantly associated with high-risk features such as tumor size, lymph node metastasis, and pathological stage. The respective diagnostic performance of FNA ( P = 0.02), BRAFV600E mutation ( P = 0.03), and ultrasonographic ( P = 0.00) findings was statistically significant. The sensitivity, specificity and positive predictive value of FNA was 64.9%, 83.3%, and 94.8%. The sensitivity, specificity and positive predictive value of BRAFV600E mutation was 56.1%, 91.7%, and 96.9% and the US features was 91.2%, 91.7%, and 98.1% respectively. However, sensitivity of FNA with BRAFV600E mutation (77.2%) was lower than FNA with US (92.9%) and combination all together (92.9%). Conclusion: In this study, we found that US features were the most useful in preoperative differential diagnosis of thyroid nodules. BRAFV600E mutation co-testing in FNA cytology was also useful for diagnosis of thyroid tumors.

BRAF V600E 돌연변이 검사를 위한 Pyrosequencing 분석법 평가

오서영,이훈택 대한임상검사과학회 2015 대한임상검사과학회지(KJCLS) Vol.47 No.1

A fine needle aspiration biopsy (FNAB) is the primary means of distinguishing benign from malignant in thyroid nodules. However, between 10 and 30% of the FNABs of thyroid nodules are diagnosed as 'indeterminate'. A molecular method is needed to reduce unnecessary surgery in this group. In Korea, most thyroid cancer is classic papillary type and BRAFV600E mutation is highly prevalent. Thus, this study compared the pyrosequencing method with the conventional direct DNA sequencing and PCR-RFLP analysis and investigated the evaluation of preoperative BRAFV600E mutation analysis as an adjunct diagnostic method with routine FNABs. Sixty-five (78.3%) of 83 histopathologically diagnosed malignant nodule revealed positive BRAFV600E mutation on pyrosequencing analysis. In detail, 65 (83.8%) of 78 papillary thyroid carcinomas sample showed positive BRAFV600E mutation. None of 29 benign nodules had in pyrodequencing, direct DNA sequencing and PCR-RFLP. Out of 31 thyroid nodules classified as 'indeterminate' on cytological examination preoperatively, 28 cases turned out to be malignant: 24 papillary thyroid carcinomas. Among that, 16 (66.7%) classic papillary thyroid carcinomas had BRAFV600E mutation. Among 65 papillary thyroid carcinomas with positive BRAFV600E mutation detected by pyrosequencing analysis, each 3 cases and 5 cases did not show BRAFV600E mutation by direct DNA sequencing and PCR-RFLP analysis. Therefore, pyrosequencing was superior to direct DNA sequencing and PCR-RFLP in detecting the BRAFV600E mutation of thyroid nodules (p =0.027). Detecting BRAFV600E mutation by pyrosequencing was more sensitivity, faster than direct DNA sequencing or PCR-RFLP.

하시모토 갑상선염을 동반한 갑상선유두암에서 BRAFV600E 돌연변이의 임상병리학적 의미

박수연,김원구,김미진,권혜미,최윤미,전민지,김태용,송영기,김원배 대한갑상선학회 2016 International Journal of Thyroidology Vol.9 No.1

Background and Objectives: The relationship between Hashimoto thyroiditis (HT) and papillary thyroid cancer (PTC) is still controversial. Some studies suggested that molecular basis of the association between HT and PTC. BRAFV600E mutation is the most common genetic alteration founded in PTC. This study was to determine a role of BRAFV600E mutation in PTC with concurrent HT and their association with other clinicopathological factors. Materials and Methods: We enrolled 452 patients who underwent thyroid surgery between 2009 and 2012 for classical PTC. The status of BRAFV600E mutation was evaluated by direct sequencing. HT was defined as presence of lymphocytic thyroiditis in pathology or positive serum anti-thyroid peroxidase antibody. Results: Total 139 patients (30%) with PTC had coexistence HT. HT was significantly associated female (p=0.006), and younger age (p=0.045). BRAFV600E mutation was confirmed in 264 patients (58%). The frequency of BRAFV600E mutation was significantly lower in PTC with coexistence HT (48.2%) compared by PTC without HT (62.9%, p=0.004). However, there was no significant difference in clinicopathological feature of PTC according to the presence of HT in patients with BRAFV600E mutated PTC. BRAFV600E mutation was less frequent in PTC with coexistence HT. Conclusion: These findings suggested that HT and BRAFV600E mutation might be independent factors in development and progression of PTC.

하시모토 갑상선염과 동반된 갑상선 유두암에서 BRAFV600E의 발현과 임상적 특징

남성진,최영식,박요한,김정훈 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.2

Background: An association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) is still controversial. Studies to date established the coexistence of HT in 11% to 36% of PTC patients. BRAFV600E mutation was presented 90% with no HT, 64% with HT in PTC patients. Therefore, BRAFV600E mutation is associated with the pathogenesis of PTC arising in HT. The purpose of this study was to identify predictive factors for the coexistence of PTC and HT and to evaluate the association of the BRAFV600E mutation with the clinicopathological features of coexistence of PTC and HT. Methods: A total of 247 patients underwent surgery for thyroid disorders between January 2007 and April 2009. In all, 212 patients was diagnosed as thyroid papillary carcinoma only (PTC group), 33 had coexistence of PTC and HT (PTC+HT group), and 2 had been diagnosed with HT. DNA was extracted from paraffin embedded thyroid tumor specimens taken from 99 patients with PTC, 13 coexistence of PTC and HT, and 2 was HT. The presence of the BRAFV600E mutation was determined by polymerase chain reaction amplification of exon 15 followed by direct sequencing. Results: Among clinicopathological features sex, age, tumor size and capsule invasion was not significant between PTC group and PTC+HT group. Lymph node metastasis and stage was significantly lower in PTC+HT group than PTC group (p=0.044). BRAFV600E mutation was found in 34 of the 99 PTC group (34.3%), 1 of the 13 PTC+HT group and 2 HT show no BRAFV600E mutation. Conclusion: These data demonstrated that the coexistence of PTC and HT was less aggressive than PTC only.

BRAF^V600E mutation in fine‐needle aspiration aspirates: Association with poorer prognostic factors in larger papillary thyroid carcinomas

Lee, Ji In,Jang, Hye Won,Kim, Sun Wook,Kim, Jong–,Won,Oh, Young Lyun,Chung, Jae Hoon Wiley Subscription Services, Inc., A Wiley Company 2013 Head & neck Vol.35 No.4

<P><B>Abstract</B></P><P><B>Background</B></P><P>Recent studies have shown that BRAF<SUP>V600E</SUP> mutation is associated with poor prognostic factors in papillary thyroid carcinoma (PTC). However, there are no studies about the association of the BRAF<SUP>V600E</SUP> mutation with poor prognostic factors according to tumor size in PTC.</P><P><B>Methods</B></P><P>We investigated the prevalence of the BRAF<SUP>V600E</SUP> mutation and its association with prognostic factors according to tumor size of PTC. BRAF<SUP>V600E</SUP> mutation status was assessed in thyroid fine‐needle aspiration (FNA) specimens from 605 patients before thyroidectomy for PTC, and its association with postoperative clinicopathologic factors was evaluated.</P><P><B>Results</B></P><P>The overall prevalence of the BRAF<SUP>V600E</SUP> mutation was 67%, and larger tumors more often had the BRAF<SUP>V600E</SUP> mutation (<I>p</I> for trend < .05). The BRAF<SUP>V600E</SUP> mutation was significantly associated with male sex, tumor size, extrathyroidal invasion, nodal metastasis, and advanced tumor stage (<I>p</I> < .05). There was a significant size‐dependent relationship between the presence of the BRAF<SUP>V600E</SUP> mutation and extrathyroidal invasion, nodal metastasis, and advanced tumor stage (<I>p</I> for trend < .05).</P><P><B>Conclusion</B></P><P>The prevalence of the BRAF<SUP>V600E</SUP> mutation increased with increased tumor size. Preoperative FNA‐detected BRAF<SUP>V600E</SUP> mutation was associated with poor prognostic factors, and the association was stronger in larger tumors. © 2012 Wiley Periodicals, Inc. Head Neck, 2013</P>

BRAFV600E Test for Suspicious Lateral Lymph Nodes in Papillary Thyroid Cancer

Wan Wook Kim,Hyang Hee Choi,Jee Yeon Lee,Seung Ook Hwang,Ho Yong Park,Ji Young Park,Jin Hyang Jung 대한갑상선-내분비외과학회 2016 The Koreran journal of Endocrine Surgery Vol.16 No.2

Purpose: This study evaluates the BRAFV600E test with fine-needle aspiration cytology (FNAC) for lateral lymph node (LN) metastasis in papillary thyroid carcinoma (PTC). Methods: Ninety-one patients, including 95 lateral LNs with possible PTC metastasis, were consecutively entered into the study. We analyzed the accuracy of results for the BRAFV600E test and FNAC for lateral LN metastasis in PTC. Results: Modified radical neck dissection was performed for 34 cases due to lateral LN metastasis. The sensitivity of FNAC was 88.2% , and the LN-BRAFV600E test 64.7%. The specificity and positive predictive value (PPV) were 100% for both tests. The negative predictive values (NPV) were FNAC, 93.8%, and LN-BRAFV600E, 83.6%. For samples positive with either the BRAFV600E test or FNAC, the sensitivity was 94.1%, specificity 100%, PPV value 100%, and NPV 96.8%. Conclusion: This study suggests that the complementary LN-BRAFV600E test with FNAC is a supportive diagnostic method for PTC patients with indeterminate or non-diagnostic suspicious lateral LNs.