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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2010

01-12-2010 | Endocrine Tumors

The BRAF Mutation Is Predictive of Aggressive Clinicopathological Characteristics in Papillary Thyroid Microcarcinoma

Authors: Kuai-Lu Lin, MD, Ou-Chen Wang, MD, Xiao-Hua Zhang, MD, Xuan-Xuan Dai, MD, Xiao-Qu Hu, MD, PhD, Jin-Miao Qu, MD

Published in: Annals of Surgical Oncology | Issue 12/2010

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Abstract

Background

This study analyzed the utility of BRAF mutation screening of ultrasonography-guided fine-needle aspiration biopsy (FNAB) specimens for predicting aggressive clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC).

Methods

We assessed the T1799A BRAF mutation status in FNAB specimens obtained from 61 PTMC patients before undergoing operations for PTMC. We examined whether the BRAF mutation was associated with clinicopathologic characteristics in PTMC. Additionally, we reviewed the BRAF mutation status, and clinical, ultrasound (US), hematological, and pathology records of the patients and analyzed the associations between these characteristics and lateral lymph node metastasis (LNM).

Results

Analysis of the preoperative FNABs accurately reflected the BRAF status of the resected tissues in 19 of the 20 paired samples (95% concordance). We observed that the BRAF mutation was statistically significantly associated with multifocality, extrathyroidal invasion, lateral LNM, and advanced tumor stages III and IV. The BRAF mutation, pathologic features (central LNM), and US features (upper pole location) were independent predictive factors for lateral LNM in a multivariate analysis with odds ratios of 18.144 (95% confidence interval [95% CI], 1.999–164.664; P = 0.01), 8.582 (95% CI, 1.014–76.662; P = 0.049) and 9.576 (95% CI, 1.374–66.728; P = 0.023), respectively.

Conclusions

BRAF mutation-positive PTMCs were more likely to manifest aggressive characteristics (extrathyroidal extension and LNM). The BRAF mutation screening of FNAB specimens can be used to predict aggressive clinicopathological characteristics of PTMC. Lateral neck nodes should be meticulously analyzed for cases of PTMC demonstrating the following three characteristics: BRAF mutation, central LNM, and US features in the upper pole location.
Literature
1.
Leenhardt L, Grosclaude P, Cherie-Challine L. Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the French Thyroid Cancer Committee. Thyroid. 2004;14:1056–60.CrossRefPubMed
2.
Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295:2164–7.CrossRefPubMed
3.
Mazzaferri EL, Harmer C, Mallick UK, et al. Practical management of thyroid cancer: a multidisciplinary approach. New York: Springer; 2006. p. 1–28.
4.
Sobin LH, Wittekind CH, editors. International Union Against Cancer (UICC): TNM classification of malignant tumors, 6th edn. New York: Wiley-Liss; 2002.
5.
Yokozawa T, Miyauchi A, Kuma K, Sugawara M. Accurate and simple method of diagnosing thyroid nodules by the modifi ed technique of ultrasound-guided fine needle aspiration biopsy. Thyroid. 1995;5:141–5.CrossRefPubMed
6.
Chow SM, Law SC, Chan JK, et al. Papillary microcarcinoma of the thyroid—prognostic significance of lymph node metastasis and multifocality. Cancer. 2003;98:31–40.CrossRefPubMed
7.
Ito Y, Miyauchi A. A therapeutic strategy for incidentally detected papillary microcarcinoma of the thyroid. Nat Clin Pract Endocrinol Metab. 2007;3:240–8.CrossRefPubMed
8.
Ito Y, Miyauchi A. Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid. Endocr J. 2003;56:177–92.CrossRef
9.
Xing MZ. BRAF mutation in papillary thyroid microcarcinoma: the promise of better risk management. Ann Surg Oncol. 2009;16:801–3.CrossRefPubMed
10.
Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007;28:742–62.CrossRefPubMed
11.
Kim TY, Kim WB, Song JY, et al. The BRAF mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma. Clin Endocrinol (Oxf). 2005;63:588–93.CrossRef
12.
Namba H, Nakashima M, Hayashi T, et al. Clinical implication of hot spot BRAF mutation V599E, in papillary thyroid cancers. J Clin Endocrinol Metab. 2003;88:4393–7.CrossRefPubMed
13.
Sedliarou I, Saenko V, Lantsov D, et al. The BRAFT1796A transversion is a prevalent mutational event in human thyroid microcarcinoma. Int J Oncol. 2004;25:1729–35.PubMed
14.
Lee X, Gao M, Ji Y, et al. Analysis of differential BRAF(V600E) mutational status in high aggressive papillary thyroid microcarcinoma. Ann Surg Oncol. 2009;16:240–5.CrossRefPubMed
15.
Kebebew E, Weng J, Bauer J, et al. The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann Surg. 2007;246:466–70.CrossRefPubMed
16.
Rodolico V, Cabibi D, Pizzolanti G, et al. BRAF(V600E) mutation and p27(kip1) expression in papillary carcinomas of the thyroid ≤1 cm and their paired lymph node metastases. Cancer. 2007;110:1218–26.CrossRefPubMed
17.
Kwak JY, Kim EK, Chung WY, et al. Association of BRAFV600E mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma. Radiology. 2009;253:854–60.CrossRefPubMed
18.
Xing MZ, Clark D, Guan H, et al. BRAF mutation testing of thyroid fine-needle aspiration biopsy specimens for preoperative risk stratification in papillary thyroid cancer. J Clin Oncol. 2009;27:2977–82.CrossRefPubMed
19.
Kwak JY, Kim EK, Kim MJ, et al. Papillary microcarcinoma of the thyroid: predicting factors of lateral neck node metastasis. Ann Surg Oncol. 2009;16:1348–55.CrossRefPubMed
20.
Ito Y, Kobayashi K, Tomoda C, et al. Illdefined edge on ultrasonographic examination can be a marker of aggressive characteristic of papillary thyroid microcarcinoma. World J Surg. 2005;29:1007–11.CrossRefPubMed
21.
Kwak JY, Kim EK, Youk JH, et al. Extrathyroid extension of well-differentiated papillary thyroid microcarcinoma on US. Thyroid. 2008;18:609–14.CrossRefPubMed
22.
Kim EK, Park CS, Chung WY, et al. New sonographic criteria for recommending fine-needle aspiration biopsy of nonpalpable solid nodules of the thyroid. AJR Am J Roentgenol. 2002;178:687–91.PubMed
23.
Gu LQ, Li FY, Zhao L, et al. BRAF(V600E) Mutation and X-linked inhibitor of apoptosis expression in papillary thyroid carcinoma. Thyroid. 2009;19:347–54.CrossRefPubMed
24.
Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS. 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. 1993;114:1050–7.PubMed
25.
Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97:418–28.CrossRefPubMed
26.
Fonseca E, Soares P, Rossi S, Sobrinho-Simoes M. Prognostic factors in thyroid carcinomas. Verh Dtsch Ges Pathol. 1997;81:82–96.PubMed
27.
Gilliland FD, Hunt WC, Morris DM, Key CR. Prognostic factors for thyroid carcinoma. A population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program, 1973–1991. Cancer. 1997;79:564–73.CrossRefPubMed
28.
Sherman SI, Brierley JD, Sperling M, et al. Prospective multicenter study of thyroid carcinoma treatment: initial analysis of staging and outcome. National Thyroid Cancer Treatment Cooperative Study Registry Group. Cancer. 1998;83:1012–21.CrossRefPubMed
29.
Ries LAG, Melbert D, Krapcho M, et al. Surveillance, epidemiology, and end results program. Cancer statistics review, 1975–2005. Bethesda: National Cancer Institute; 2008.
30.
Ito Y, Uruno T, Nakano K, et al. 2003 An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 13:381–8.CrossRefPubMed
31.
32.
Brown AP, Chen J, Hitchcock YJ, et al. The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab. 2008;93:504–15.CrossRefPubMed
33.
Jin L, Sebo TJ, Nakamura N, et al. BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid. Diagn Mol Pathol. 2006;15:136–43.CrossRefPubMed
34.
Chung KW, Yang SK, Lee GK, et al. Detection of BRAFV600E mutation on fine needle aspiration specimens of thyroid nodule refines cyto-pathology diagnosis, especially in BRAF600E mutation-prevalent area. Clin Endocrinol (Oxf). 2006;65:660–6.CrossRef
35.
Pizzolanti G, Russo L, Richiusa P, et al. Fine-needle aspiration molecular analysis for the diagnosis of papillary thyroid carcinoma through BRAF(V600E) mutation and RET/PTC rearrangement. Thyroid. 2007;17:1109–15.CrossRefPubMed
36.
Rowe LR, Bentz BG, Bentz JS. Utility of BRAF V600E mutation detection in cytologically indeterminate thyroid nodules. Cytojournal. 2006;3:10.CrossRefPubMed
37.
Bramley MD, Harrison BJ. Papillary microcarcinoma of the thyroid gland. Br J Surg. 1996;83:1674–83.CrossRefPubMed
38.
Harach HR, Franssila KO, Wasenius VM. Occult papillary carcinoma of the thyroid “normal” finding in Finland—a systematic autopsy study. Cancer. 1985;56:531–8.CrossRefPubMed
39.
Pelizzo MR, Boschin IM, Toniato A, et al. Natural history, diagnosis, treatment and outcome of papillary thyroid microcarcinoma (PTMC): a mono-institutional 12-year experience. Nucl Med Commun. 2004;25:547–52.CrossRefPubMed
40.
Shaha AR. Thyroid cancer: extent of thyroidectomy. Cancer Control. 2000;7:240–5.PubMed
41.
McHenry CR, Rosen IB, Walfish PG. Prospective management of nodal metastases in differentiated thyroid cancer. Am J Surg. 1991;162:353–6.CrossRefPubMed
42.
Akslen LA, Haldorsen T, Thoresen SO, Glattre E. Survival and causes of death in thyroid cancer: a population-based study of 2479 cases from Norway. Cancer Res. 1991;51:1234–41.PubMed
43.
Ito Y, Miyauchi A. Lateral lymph node dissection guided by preoperative and intraoperative findings in differentiated thyroid carcinoma. World J Surg. 2008;32:729–39.CrossRefPubMed
44.
Wang YG, Ji MJ, Wang W, et al. Association of the T1799A BRAF mutation with tumor extrathyroidal invasion, higher peripheral platelet counts, and overexpression of platelet-derived growth factor-B in papillary thyroid cancer. Endocr Relat Cancer. 2008;15:183–90.CrossRefPubMed
45.
Hernandez E, Donohue KA, Anderson LL, Heller PB, Stehman FB. The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000;78:137–42.CrossRefPubMed
46.
Ikeda M, Furukawa H, Imamura H, et al. Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol. 2002;9:287–91.CrossRefPubMed
47.
Verheul HM, Pinedo HM. The importance of platelet counts and their contents in cancer. Clin Cancer Res. 2003;9;3219–21.PubMed
48.
Shimada H, Oohira G, Okazumi S, et al. Thrombocytosis associated with poor prognosis in patients with esophageal carcinoma. J Am Coll Surg. 2004;198;737–41.CrossRefPubMed
49.
Brown KM, Domin C, Aranha GV, Yong S, Shoup M. Increased preoperative platelet count is associated with decreased survival after resection for adenocarcinoma of the pancreas. Am J Surg. 2005;189:278–82.CrossRefPubMed
50.
Bensalah K, Leray E, Fergelot P, et al. Prognostic value of thrombocytosis in renal cell carcinoma. J Urol. 2006;175:859–63.CrossRefPubMed
51.
Ito Y, Tomoda C, Uruno T, et al. Papillary microcarcinoma of the thyroid: how should it be treated? World J Surg. 2004;28:1115–21.CrossRefPubMed
Metadata
Title
The BRAF Mutation Is Predictive of Aggressive Clinicopathological Characteristics in Papillary Thyroid Microcarcinoma
Authors
Kuai-Lu Lin, MD
Ou-Chen Wang, MD
Xiao-Hua Zhang, MD
Xuan-Xuan Dai, MD
Xiao-Qu Hu, MD, PhD
Jin-Miao Qu, MD
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1129-6

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