Original Article

Initial clinical experience with BRAF^V600E mutation analysis of core-needle biopsy specimens from thyroid nodules

Sang Hyun Choi

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Jung Hwan Baek,

Corresponding Author

Jung Hwan Baek

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Correspondence: Jung Hwan Baek, Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Songpa-gu, Seoul 138-736, Korea. Tel.: 82 2 3010 4348; Fax: 82 2 476 0090; E-mail: [email protected]Search for more papers by this author

Jeong Hyun Lee,

Jeong Hyun Lee

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Young Jun Choi,

Young Jun Choi

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Eun Ju Ha,

Eun Ju Ha

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Department of Radiology, Ajou University School of Medicine, Yeongtong-Gu, Suwon, Korea

Search for more papers by this author

Dong Eun Song,

Dong Eun Song

Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Jae Kyun Kim,

Jae Kyun Kim

Department of Radiology, Chung-Ang University College of Medicine, Dongjak-gu, Seoul, Korea

Search for more papers by this author

Ki-Wook Chung,

Ki-Wook Chung

Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Tae Yong Kim,

Tae Yong Kim

Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Won Bae Kim,

Won Bae Kim

Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Young Kee Shong,

Young Kee Shong

Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Sang Hyun Choi,

Sang Hyun Choi

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Jung Hwan Baek,

Corresponding Author

Jung Hwan Baek

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Jeong Hyun Lee,

Jeong Hyun Lee

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Young Jun Choi,

Young Jun Choi

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Eun Ju Ha,

Eun Ju Ha

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Department of Radiology, Ajou University School of Medicine, Yeongtong-Gu, Suwon, Korea

Search for more papers by this author

Dong Eun Song,

Dong Eun Song

Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Jae Kyun Kim,

Jae Kyun Kim

Department of Radiology, Chung-Ang University College of Medicine, Dongjak-gu, Seoul, Korea

Search for more papers by this author

Ki-Wook Chung,

Ki-Wook Chung

Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Tae Yong Kim,

Tae Yong Kim

Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Won Bae Kim,

Won Bae Kim

Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

Young Kee Shong,

Young Kee Shong

Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea

Search for more papers by this author

First published: 27 July 2015

https://doi.org/10.1111/cen.12866

Citations: 5

Share a link

Email
Wechat
Bluesky

Summary

Objective

The accurate diagnosis of thyroid nodules is important for making management decisions. The purpose of this study was to evaluate the feasibility of core-needle biopsy with BRAF^V600E mutation analysis (CNB + BRAF^V600E) and to compare the clinical usefulness of CNB + BRAF^V600E and fine-needle aspiration with BRAF^V600E mutation analysis (FNA + BRAF^V600E) in the diagnosis of thyroid malignancy.

Design, patients and measurements

The results of BRAF^V600E mutation analyses of 820 nodules from 820 patients (153 men, 667 women; mean age, 51·1 years), who underwent CNB + BRAF^V600E (n = 256) or FNA + BRAF^V600E (n = 564) between January 2011 and March 2012 were retrospectively evaluated. The feasibility of CNB + BRAF^V600E was assessed by comparing its rate of detection of BRAF^V600E mutations and positive predictive value with those of FNA + BRAF^V600E. The clinical usefulness of CNB + BRAF^V600E was determined by comparing rates of inconclusive results, the additional value of BRAF^V600E mutation analysis, diagnostic surgery and diagnostic performance with those of FNA + BRAF^V600E.

Results

CNB + BRAF^V600E and FNA + BRAF^V600E had similar rates of BRAF^V600E mutation detection (66·3% vs 64·4%, P = 0·883) and positive predictive value (100·0% vs 96·6%, P = 0·135). CNB + BRAF^V600E had a significantly higher diagnostic accuracy rate (95·7% vs 85·9%, P < 0·001), and significantly lower rates of inconclusive results (8·2% vs 51·8%, P < 0·001), and diagnostic surgery (8·9% vs 22·3%, P = 0·006), than FNA + BRAF^V600E.

Conclusions

The greater diagnostic performance of CNB + BRAF^V600E and its lower rate of inconclusive results than FNA + BRAF^V600E suggest that CNB + BRAF^V600E can reduce rates of preventable diagnostic surgery.

References

1Wang, C.C., Friedman, L., Kennedy, G.C. et al. (2011) A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid, 21, 243–251.
10.1089/thy.2010.0243
PubMed Web of Science® Google Scholar
2Alexander, E.K., Heering, J.P., Benson, C.B. et al. (2002) Assessment of nondiagnostic ultrasound-guided fine needle aspirations of thyroid nodules. Journal of Clinical Endocrinology and Metabolism, 87, 4924–4927.
10.1210/jc.2002-020865
CAS PubMed Web of Science® Google Scholar
3Baier, N.D., Hahn, P.F., Gervais, D.A. et al. (2009) Fine-needle aspiration biopsy of thyroid nodules: experience in a cohort of 944 patients. AJR. American Journal of Roentgenology, 193, 1175–1179.
10.2214/AJR.08.1840
PubMed Web of Science® Google Scholar
4Carmeci, C., Jeffrey, R.B., McDougall, I.R. et al. (1998) Ultrasound-guided fine-needle aspiration biopsy of thyroid masses. Thyroid, 8, 283–289.
10.1089/thy.1998.8.283
CAS PubMed Web of Science® Google Scholar
5Gharib, H., Goellner, J.R., Zinsmeister, A.R. et al. (1984) Fine-needle aspiration biopsy of the thyroid. The problem of suspicious cytologic findings. Annals of Internal Medicine, 101, 25–28.
10.7326/0003-4819-101-1-25
CAS PubMed Web of Science® Google Scholar
6Kim, S.K., Kim, D.L., Han, H.S. et al. (2008) Pyrosequencing analysis for detection of a BRAFV600E mutation in an FNAB specimen of thyroid nodules. Diagnostic Molecular Pathology, 17, 118–125.
10.1097/PDM.0b013e31815d059d
CAS PubMed Web of Science® Google Scholar
7Moon, W.J., Choi, N., Choi, J.W. et al. (2012) BRAF mutation analysis and sonography as adjuncts to fine-needle aspiration cytology of papillary thyroid carcinoma: their relationships and roles. AJR. American Journal of Roentgenology, 198, 668–674.
10.2214/AJR.11.7185
PubMed Web of Science® Google Scholar
8Nam, S.Y., Han, B.K., Ko, E.Y. et al. (2010) BRAF V600E mutation analysis of thyroid nodules needle aspirates in relation to their ultrasongraphic classification: a potential guide for selection of samples for molecular analysis. Thyroid, 20, 273–279.
10.1089/thy.2009.0226
CAS PubMed Web of Science® Google Scholar
9Nikiforov, Y.E., Steward, D.L., Robinson-Smith, T.M. et al. (2009) Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. Journal of Clinical Endocrinology and Metabolism, 94, 2092–2098.
10.1210/jc.2009-0247
CAS PubMed Web of Science® Google Scholar
10Musholt, T.J., Fottner, C., Weber, M.M. et al. (2010) Detection of papillary thyroid carcinoma by analysis of BRAF and RET/PTC1 mutations in fine-needle aspiration biopsies of thyroid nodules. World Journal of Surgery, 34, 2595–2603.
10.1007/s00268-010-0729-4
PubMed Web of Science® Google Scholar
11Kim, S.K., Hwang, T.S., Yoo, Y.B. et al. (2011) Surgical results of thyroid nodules according to a management guideline based on the BRAF(V600E) mutation status. Journal of Clinical Endocrinology and Metabolism, 96, 658–664.
10.1210/jc.2010-1082
CAS PubMed Web of Science® Google Scholar
12Lee, S.T., Kim, S.W., Ki, C.S. et al. (2012) Clinical implication of highly sensitive detection of the BRAF V600E mutation in fine-needle aspirations of thyroid nodules: a comparative analysis of three molecular assays in 4585 consecutive cases in a BRAF V600E mutation-prevalent area. Journal of Clinical Endocrinology and Metabolism, 97, 2299–2306.
10.1210/jc.2011-3135
CAS PubMed Web of Science® Google Scholar
13Na, D.G., Kim, J.H., Sung, J.Y. et al. (2012) Core-needle biopsy is more useful than repeat fine-needle aspiration in thyroid nodules read as nondiagnostic or atypia of undetermined significance by the Bethesda system for reporting thyroid cytopathology. Thyroid, 22, 468–475.
10.1089/thy.2011.0185
PubMed Web of Science® Google Scholar
14Yeon, J.S., Baek, J.H., Lim, H.K. et al. (2013) Thyroid nodules with initially nondiagnostic cytologic results: the role of core-needle biopsy. Radiology, 268, 274–280.
10.1148/radiol.13122247
PubMed Web of Science® Google Scholar
15Choi, Y.J., Baek, J.H., Ha, E.J. et al. (2014) Differences in risk of malignancy and management recommendations in subcategories of thyroid nodules with atypia of undetermined significance or follicular lesion of undetermined significance: the role of ultrasound-guided core-needle biopsy. Thyroid, 24, 494–501.
10.1089/thy.2012.0635
PubMed Web of Science® Google Scholar
16Screaton, N.J., Berman, L.H. & Grant, J.W. (2003) US-guided core-needle biopsy of the thyroid gland. Radiology, 226, 827–832.
10.1148/radiol.2263012073
PubMed Web of Science® Google Scholar
17Baloch, Z.W., Cibas, E.S., Clark, D.P. et al. (2008) The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. CytoJournal, 5, 6.
10.1186/1742-6413-5-6
PubMed Web of Science® Google Scholar
18Sung, J.Y., Na, D.G., Kim, K.S. et al. (2012) Diagnostic accuracy of fine-needle aspiration versus core-needle biopsy for the diagnosis of thyroid malignancy in a clinical cohort. European Radiology, 22, 1564–1572.
10.1007/s00330-012-2405-6
PubMed Web of Science® Google Scholar
19Choi, S.H., Baek, J.H., Lee, J.H. et al. (2014) Thyroid nodules with initially non-diagnostic, fine-needle aspiration results: comparison of core-needle biopsy and repeated fine-needle aspiration. European Radiology, 24, 2819–2826.
10.1007/s00330-014-3325-4
PubMed Web of Science® Google Scholar
20Kwak, J.Y., Jung, I., Baek, J.H. et al. (2013) Image reporting and characterization system for ultrasound features of thyroid nodules: multicentric korean retrospective study. Korean Journal of Radiology, 14, 110–117.
10.3348/kjr.2013.14.1.110
PubMed Web of Science® Google Scholar
21Cibas, E.S. & Ali, S.Z. (2009) The Bethesda system for reporting thyroid cytopathology. Thyroid, 19, 1159–1165.
10.1089/thy.2009.0274
PubMed Web of Science® Google Scholar
22Lee, H.J., Choi, J., Hwang, T.S. et al. (2010) Detection of BRAF mutations in thyroid nodules by allele-specific PCR using a dual priming oligonucleotide system. American Journal of Clinical Pathology, 133, 802–808.
10.1309/AJCPO3F2ENKMDTUS
CAS PubMed Web of Science® Google Scholar
23Chung, K.W., Yang, S.K., Lee, G.K. et al. (2006) Detection of BRAFV600E mutation on fine needle aspiration specimens of thyroid nodule refines cyto-pathology diagnosis, especially in BRAF600E mutation-prevalent area. Clinical Endocrinology, 65, 660–666.
10.1111/j.1365-2265.2006.02646.x
CAS PubMed Web of Science® Google Scholar
24Moon, H.J., Kim, E.K., Chung, W.Y. et al. (2011) Diagnostic value of BRAF(V600E) mutation analysis of thyroid nodules according to ultrasonographic features and the time of aspiration. Annals of Surgical Oncology, 18, 792–799.
10.1245/s10434-010-1354-z
PubMed Web of Science® Google Scholar
25Crescenzi, A., Guidobaldi, L., Nasrollah, N. et al. (2014) Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers. Hormone and Metabolic Research, 46, 370–374.
10.1055/s-0034-1368700
CAS PubMed Web of Science® Google Scholar
26Lee, S.H., Kim, M.H., Bae, J.S. et al. (2014) Clinical outcomes in patients with non-diagnostic thyroid fine needle aspiration cytology: usefulness of the thyroid core needle biopsy. Annals of Surgical Oncology, 21, 1870–1877.
10.1245/s10434-013-3365-z
PubMed Web of Science® Google Scholar
27Gharib, H., Papini, E., Paschke, R. et al. (2010) American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and EuropeanThyroid Association Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocrine Practice: Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 16(Suppl 1), 1–43.
10.4158/10024.GL
PubMed Google Scholar
28Cooper, D.S., Doherty, G.M., Haugen, B.R. et al. (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 19, 1167–1214.
10.1089/thy.2009.0110
PubMed Web of Science® Google Scholar
29Gavrila, A. (2011) A review of the diagnostic accuracy of thyroid fine needle aspiration biopsy. Clinical Thyroidology for The public, 4, 7–8.
Google Scholar
30Ha, E.J., Baek, J.H., Lee, J.H. et al. (2014) Core needle biopsy can minimise the non-diagnostic results and need for diagnostic surgery in patients with calcified thyroid nodules. European Radiology, 24, 1403–1409.
10.1007/s00330-014-3123-z
PubMed Web of Science® Google Scholar

Citing Literature

Volume84, Issue4

April 2016

Pages 607-613

Initial clinical experience with BRAF^V600E mutation analysis of core-needle biopsy specimens from thyroid nodules

Summary

Objective

Design, patients and measurements

Results

Conclusions

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Initial clinical experience with BRAFV600E mutation analysis of core-needle biopsy specimens from thyroid nodules

Summary

Objective

Design, patients and measurements

Results

Conclusions

References

Citing Literature

References

Related

Information

Initial clinical experience with BRAF^V600E mutation analysis of core-needle biopsy specimens from thyroid nodules