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Published in: World Journal of Surgery 8/2020

01-08-2020 | Thyroidectomy | Original Scientific Report

BRAFV600E Mutation is Associated with an Increased Risk of Papillary Thyroid Cancer Recurrence

Authors: Samuel Enumah, Abbey Fingeret, Sareh Parangi, Dora Dias-Santagata, Peter M. Sadow, Carrie C. Lubitz

Published in: World Journal of Surgery | Issue 8/2020

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Abstract

Background

Papillary thyroid carcinoma is the most common endocrine malignancy and one of the most common cancers worldwide. However, the optimal timing and frequency of surveillance to assess for recurrence remain undetermined. As the incidence of thyroid cancer continues to rise worldwide, identifying risk factors for recurrence and investigating intervals and durations of surveillance are paramount to adapt treatment and follow-up plans to high-risk individuals and to reduce interventions for low-risk patients.

Methods

Our dataset included an unselected cohort of papillary thyroid carcinoma (PTC) patients who underwent a total thyroidectomy (or unilateral then completion thyroidectomy) at a single institution from 2000 to 2007. BRAF genotyping was performed on available specimens by a validated PCR-based assay. Pathologic structural recurrence was the primary outcome. We performed univariate and multivariable analyses to identify predictors of cancer recurrence.

Results

In total, 599 patients underwent complete resection of the thyroid gland for PTC. The cohort was young (mean age 45.0 years), predominately female (n = 462, 76.9%), and median follow-up was 10.3 years (IQR 5.4–12.2). Recurrence occurred more commonly in the BRAFV600E group (18.6 vs. 9.9%, p = 0.02). BRAF independently predicted PTC recurrence (HR 2.81, p = 0.006).

Conclusions

BRAF mutation is an independent predictor of papillary thyroid carcinoma long-term recurrence. Understanding molecular characteristics of individual thyroid cancers may help risk-stratify patients and direct them toward more appropriate initial care and long-term surveillance strategies.
Literature
1.
go back to reference Pellegriti G, Frasca F, Regalbuto C et al (2013) Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol 2013:965212CrossRef Pellegriti G, Frasca F, Regalbuto C et al (2013) Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol 2013:965212CrossRef
2.
go back to reference Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108CrossRef Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108CrossRef
3.
go back to reference Grogan RH, Kaplan SP, Cao H et al (2013) A study of recurrence and death from papillary thyroid cancer with 27 years of median follow-up. Surgery 154:1436–1437CrossRef Grogan RH, Kaplan SP, Cao H et al (2013) A study of recurrence and death from papillary thyroid cancer with 27 years of median follow-up. Surgery 154:1436–1437CrossRef
4.
go back to reference Haugen BR, Alexander EK, Bible KC et al (2016) 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26:1–133CrossRef Haugen BR, Alexander EK, Bible KC et al (2016) 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26:1–133CrossRef
5.
go back to reference Xing M (2005) BRAF mutation in thyroid cancer. Endocr Relat Cancer 12:245–262CrossRef Xing M (2005) BRAF mutation in thyroid cancer. Endocr Relat Cancer 12:245–262CrossRef
6.
go back to reference Xing M (2007) BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 28:742–762CrossRef Xing M (2007) BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 28:742–762CrossRef
7.
go back to reference Pak K, Suh S, Kim SJ, Kim I-J (2015) Prognostic value of genetic mutations in thyroid cancer: a meta-analysis. Thyroid 25:63–70CrossRef Pak K, Suh S, Kim SJ, Kim I-J (2015) Prognostic value of genetic mutations in thyroid cancer: a meta-analysis. Thyroid 25:63–70CrossRef
8.
go back to reference Xing M, Alzahrani AS, Carson KA et al (2013) Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 309:1493–1501CrossRef Xing M, Alzahrani AS, Carson KA et al (2013) Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 309:1493–1501CrossRef
9.
go back to reference Xing M, Alzahrani AS, Carson KA et al (2015) Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol 33:42–50CrossRef Xing M, Alzahrani AS, Carson KA et al (2015) Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol 33:42–50CrossRef
10.
go back to reference Lin AJ, Samson P, DeWees T et al (2019) A molecular approach combined with American Thyroid Association classification better stratifies recurrence risk of classic histology papillary thyroid cancer. Cancer Med 8:437–446PubMed Lin AJ, Samson P, DeWees T et al (2019) A molecular approach combined with American Thyroid Association classification better stratifies recurrence risk of classic histology papillary thyroid cancer. Cancer Med 8:437–446PubMed
11.
go back to reference Henke LE, Pfeifer JD, Ma C et al (2015) BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma. Cancer Med 4:791–799CrossRef Henke LE, Pfeifer JD, Ma C et al (2015) BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma. Cancer Med 4:791–799CrossRef
12.
go back to reference Barbaro D, Incensati RM, Materazzi G et al (2014) The BRAF V600E mutation in papillary thyroid cancer with positive or suspected pre-surgical cytological finding is not associated with advanced stages or worse prognosis. Endocrine 45:462–468CrossRef Barbaro D, Incensati RM, Materazzi G et al (2014) The BRAF V600E mutation in papillary thyroid cancer with positive or suspected pre-surgical cytological finding is not associated with advanced stages or worse prognosis. Endocrine 45:462–468CrossRef
13.
go back to reference Gouveia C, Can NT, Bostrom A et al (2013) Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma: the University of California, San Francisco, experience. JAMA Otolaryngol Head Neck Surg 139:1164–1170CrossRef Gouveia C, Can NT, Bostrom A et al (2013) Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma: the University of California, San Francisco, experience. JAMA Otolaryngol Head Neck Surg 139:1164–1170CrossRef
14.
go back to reference Hay ID, Bergstralh EJ, Goellner JR et al (1993) Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 114:1050–1058PubMed Hay ID, Bergstralh EJ, Goellner JR et al (1993) Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 114:1050–1058PubMed
15.
go back to reference Sanders LE, Cady B (1998) Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg 133:419–425CrossRef Sanders LE, Cady B (1998) Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg 133:419–425CrossRef
16.
go back to reference Cooper DS, Doherty GM, Haugen BR et al (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214CrossRef Cooper DS, Doherty GM, Haugen BR et al (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214CrossRef
17.
go back to reference Lee SG, Lee WK, Lee HS et al (2017) Practical performance of the 2015 American Thyroid Association guidelines for predicting tumor recurrence in patients with papillary thyroid cancer in South Korea. Thyroid 27:174–181CrossRef Lee SG, Lee WK, Lee HS et al (2017) Practical performance of the 2015 American Thyroid Association guidelines for predicting tumor recurrence in patients with papillary thyroid cancer in South Korea. Thyroid 27:174–181CrossRef
18.
go back to reference Prescott JD, Sadow PM, Hodin RA et al (2012) BRAF V600E status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence. Surgery 152:984–990CrossRef Prescott JD, Sadow PM, Hodin RA et al (2012) BRAF V600E status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence. Surgery 152:984–990CrossRef
19.
go back to reference Cohen Y, Xing M, Mambo E et al (2003) BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 95:625–627CrossRef Cohen Y, Xing M, Mambo E et al (2003) BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 95:625–627CrossRef
20.
go back to reference Niederer-Wust SM, Jochum W, Forbs D et al (2015) Impact of clinical risk scores and BRAF V600E mutation status on outcome in papillary thyroid cancer. Surgery 157:119–125CrossRef Niederer-Wust SM, Jochum W, Forbs D et al (2015) Impact of clinical risk scores and BRAF V600E mutation status on outcome in papillary thyroid cancer. Surgery 157:119–125CrossRef
21.
go back to reference Chen Y, Sadow PM, Suh H et al (2016) BRAF(V600E) is correlated with recurrence of papillary thyroid microcarcinoma: a systematic review, multi-institutional primary data analysis, and meta-analysis. Thyroid 26:248–255CrossRef Chen Y, Sadow PM, Suh H et al (2016) BRAF(V600E) is correlated with recurrence of papillary thyroid microcarcinoma: a systematic review, multi-institutional primary data analysis, and meta-analysis. Thyroid 26:248–255CrossRef
22.
go back to reference Routhier CA, Mochel MC, Lynch K et al (2013) Comparison of 2 monoclonal antibodies for immunohistochemical detection of BRAF V600E mutation in malignant melanoma, pulmonary carcinoma, gastrointestinal carcinoma, thyroid carcinoma, and gliomas. Hum Pathol 44:2563–2570CrossRef Routhier CA, Mochel MC, Lynch K et al (2013) Comparison of 2 monoclonal antibodies for immunohistochemical detection of BRAF V600E mutation in malignant melanoma, pulmonary carcinoma, gastrointestinal carcinoma, thyroid carcinoma, and gliomas. Hum Pathol 44:2563–2570CrossRef
23.
go back to reference Vuong HG, Altibi AMA, Duong UNP, Hassell L (2017) Prognostic implication of BRAF and TERT promoter mutation combination in papillary thyroid carcinoma—a meta-analysis. Clin Endocrinol (Oxf) 87:411–417CrossRef Vuong HG, Altibi AMA, Duong UNP, Hassell L (2017) Prognostic implication of BRAF and TERT promoter mutation combination in papillary thyroid carcinoma—a meta-analysis. Clin Endocrinol (Oxf) 87:411–417CrossRef
24.
go back to reference Durante C, Montesano T, Torlontano M et al (2013) Papillary thyroid cancer: time course of recurrences during postsurgery surveillance. J Clin Endocrinol Metab 98:636–642CrossRef Durante C, Montesano T, Torlontano M et al (2013) Papillary thyroid cancer: time course of recurrences during postsurgery surveillance. J Clin Endocrinol Metab 98:636–642CrossRef
25.
go back to reference Brassard M, Borget I, Edet-Sanson A et al (2011) Long-term follow-up of patients with papillary and follicular thyroid cancer: a prospective study on 715 patients. J Clin Endocrinol Metab 96:1352–1359CrossRef Brassard M, Borget I, Edet-Sanson A et al (2011) Long-term follow-up of patients with papillary and follicular thyroid cancer: a prospective study on 715 patients. J Clin Endocrinol Metab 96:1352–1359CrossRef
Metadata
Title
BRAFV600E Mutation is Associated with an Increased Risk of Papillary Thyroid Cancer Recurrence
Authors
Samuel Enumah
Abbey Fingeret
Sareh Parangi
Dora Dias-Santagata
Peter M. Sadow
Carrie C. Lubitz
Publication date
01-08-2020
Publisher
Springer International Publishing
Published in
World Journal of Surgery / Issue 8/2020
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-020-05521-2

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