Correlation Between BRAF<sup>V600E</sup> Gene Mutation and The Prognostic Factors in Papillary Thyroid Microcarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 SUNYu , SHITie-feng , YUJiang-tao ,  SHIChen-lei , QINHua-dong

The Fourth Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China;

Corresponding author：

SHIChen-lei, Email: aitiantang83@126.com

Keywords：

Papillary thyroid microarcinoma; BRAF gene; Gene mutation; Lymph node metastases

DOI：

10.7507/1007-9424.20140294

Video：

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Objective To investigate the relationship of concomitant BRAF^V600E gene mutation with the predictive factors of papillay thyroid microcarcinoma(PTMC). Methods By fluorescence quantitative PCR method to detect BRAF^V600E gene mutation of PTMC of 86 cases, and to detect the relationship with clinical pathological features of PTMC by single factor and multi-factor logistic regression analysis. Results The morbidity of BRAF^V600E gene mutation was 65.1%(56/86). By univariate analysis, BRAF^V600E gene mutation status showed a related trend with lymph node metastasis(P=0.057). The multivariate analysis showwd that lymph node metastasis was correlated with BRAF V600E gene mutation(P < 0.05). When the diameter of tumor > 5 mm and≤10mm, BRAF^V600E gene mutation was no statistically significantly related to central lymph node metastasis(P > 0.05). When BRAF^V600E gene mutations was negative in patients with tumor diameter≤5 mm, no lymph node metastasis sample appeared. Conclusions The presence of BRAF^V600E gene mutation is an independent predictive factor for central lymph node metastasis. When PTC with preoperative BRAF^V600E gene mutation positive, the central neck dissection should be routine performed. There should be re-examined the necessity of preventative central lymph node disection when the tumor diameter is 5 mm or less with the patients which mutation negative.

Citation： SUNYu, SHITie-feng, YUJiang-tao, SHIChen-lei, QINHua-dong. Correlation Between BRAF^V600E Gene Mutation and The Prognostic Factors in Papillary Thyroid Microcarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(10): 1226-1231. doi: 10.7507/1007-9424.20140294 Copy

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15.	Park SY, Park YJ, Lee YJ, et al. Analysis of differential BRAF^V600E mutational status in multifocal papillary thyroid carci-noma:evidence of independent clonal origin in distinct tumor foci[J]. Cancer, 2006, 107(8):1831-1838.
16.	Xing M. BRAF mutation in thyroid cancer[J]. Endocr Relat Cancer, 2005, 12(2):245-262.
17.	Zheng X, Wei S, Han Y, et al. Papillary microcarcinoma of the thyroid:clinical characteristics and BRAF^V600E mutational status of 977 cases[J]. Ann Surg Oncol, 2013, 20(7):2266-2273.
18.	石臣磊, 秦华东.乳头状甲状腺癌与BRAF基因相关性的最新研究进展[J].中国普通外科杂志, 2014, 5(23):675-679.
19.	Lin KL, Wang OC, Zhang XH, et al. The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma[J]. Ann Surg Oncol, 2010, 17(12):3294-3300.
20.	Cheng S, Serra S, Mercado M, et al. A high-throughput prot-eomic approach provides distinct signatures for thyroid cancer behavior[J]. Clin Cancer Res, 2011, 17(8):2385-2394.
21.	Alzahrani AS, Xing M. Impact of lymph node metastases identified on central neck dissection (CND) on the recurrence of papillary thyroid cancer:potential role of BRAFV600E mutation in defining CND[J]. Endocr Relat Cancer, 2013, 20(1):13-22.
22.	Joo JY, Park JY, Yoon YH, et al. Prediction of occult central lymph node metastasis in papillary thyroid carcinoma by preoper-ative BRAF analysis using fine-needle aspiration biopsy:a prospective study[J]. J Clin Endocrinol Metab, 2012, 97(11):3996-4003.
23.	石臣磊, 石铁锋, 秦华东.乳头状甲状腺癌颈淋巴结转移方式及其相关影响因素的研究[J].中国普外基础与临床杂志, 2014, 1(21):29-34.
24.	Wang Q, Chu B, Zhu J, et al. Clinical analysis of prophylactic central neck dissection for papillary thyroid carcinoma[J]. Clin Transl Oncol, 2014, 16(1):44-48.
25.	Wang TS, Cheung K, Farrokhyar F, et al. A meta-analysis of the effect of prophylactic central compartment neck dissection on locoregional recurrence rates in patients with papillary thyroid cancer[J]. Ann Surg Oncol, 2013, 20(11):3477-3483.

1. Hedinger C, Williams ED, Sobin LH. The WHO histological classification of thyroid tumors:a commentary on the second edition[J]. Cancer, 1989, 63(5):908-911.
2. Kilfoy BA, Zheng T, Holford TR, et al. International patterns and trends in thyroid cancer incidence, 1973-2002[J]. Cancer Causes Control, 2009, 20(5):525-531.
3. Plzák J, Astl J, Psychogios G, et al. Current treatment strategies for papillary thyroid microcarcinoma[J]. HNO, 2013, 61(4):300-305.
4. Wu LS, Milan SA. Management of microcarcinomas (papillary and medullary) of the thyroid[J]. Curr Opin Oncol, 2013, 25(1):27-32.
5. Kim KH, Kang DW, Kim SH, et al. Mutations of the BRAF gene in papillary thyroid carcinoma in a Korean population[J]. Yonsei Med J, 2004, 45(5):818-821.
6. Chakraborty A, Narkar A, Mukhopadhyaya R, et al. BRAF V600E mutation in papillary thyroid carcinoma:significant asso-ciation with node metastases and extra thyroidal invasion[J]. Endocr Pathol, 2012, 23(2):83-93.
7. Mathur A, Moses W, Rahbari R, et al. Higher rate of BRAF mutation in papillary thyroid cancer over time:a single-institution study[J]. Cancer, 2011, 117(19):4390-4395.
8. Nucera C, Lawler J, Hodin R, et al. The BRAFV600E mutation:what is it really orchestrating in thyroid cancer?[J]. Oncotarget, 2010, 1(8):751-756.
9. Li Y, Nakamura M, Kakudo K. Targeting of the BRAF gene in papillary thyroid carcinoma (review)[J]. Oncol Rep, 2009, 22(4):671-681.
10. Lopes JP, Fonseca E. BRAF gene mutation in the natural history of papillary thyroid carcinoma:diagnostic and prognostic implications[J]. Acta Med Port, 2011, 24(4):855-868.
11. Stratmann M, Sekulla C, Dralle H, et al. Current TNM system of the UICC/AJCC:the prognostic significance for differentiated thyroid carcinoma[J]. Chirurg, 2012, 83(7):646-651.
12. Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia[J]. Nat Rev, 2006, 6(4):292-306.
13. Chow SM, Law SC, Chan JKC, et al. Papillary microcarcinoma of the thyroid-prognostic significance of lymph node metastasis and multifocality[J]. Cancer, 2003, 98(1):31-40.
14. Lee X, Gao M, Ji Y, et al. Analysis of differential BRAFV600E mutational status in high aggressive papillary thyroid microcarcinoma[J]. Ann Surg Oncol, 2009, 16(2):240-245.
15. Park SY, Park YJ, Lee YJ, et al. Analysis of differential BRAF^V600E mutational status in multifocal papillary thyroid carci-noma:evidence of independent clonal origin in distinct tumor foci[J]. Cancer, 2006, 107(8):1831-1838.
16. Xing M. BRAF mutation in thyroid cancer[J]. Endocr Relat Cancer, 2005, 12(2):245-262.
17. Zheng X, Wei S, Han Y, et al. Papillary microcarcinoma of the thyroid:clinical characteristics and BRAF^V600E mutational status of 977 cases[J]. Ann Surg Oncol, 2013, 20(7):2266-2273.
18. 石臣磊, 秦华东.乳头状甲状腺癌与BRAF基因相关性的最新研究进展[J].中国普通外科杂志, 2014, 5(23):675-679.
19. Lin KL, Wang OC, Zhang XH, et al. The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma[J]. Ann Surg Oncol, 2010, 17(12):3294-3300.
20. Cheng S, Serra S, Mercado M, et al. A high-throughput prot-eomic approach provides distinct signatures for thyroid cancer behavior[J]. Clin Cancer Res, 2011, 17(8):2385-2394.
21. Alzahrani AS, Xing M. Impact of lymph node metastases identified on central neck dissection (CND) on the recurrence of papillary thyroid cancer:potential role of BRAFV600E mutation in defining CND[J]. Endocr Relat Cancer, 2013, 20(1):13-22.
22. Joo JY, Park JY, Yoon YH, et al. Prediction of occult central lymph node metastasis in papillary thyroid carcinoma by preoper-ative BRAF analysis using fine-needle aspiration biopsy:a prospective study[J]. J Clin Endocrinol Metab, 2012, 97(11):3996-4003.
23. 石臣磊, 石铁锋, 秦华东.乳头状甲状腺癌颈淋巴结转移方式及其相关影响因素的研究[J].中国普外基础与临床杂志, 2014, 1(21):29-34.
24. Wang Q, Chu B, Zhu J, et al. Clinical analysis of prophylactic central neck dissection for papillary thyroid carcinoma[J]. Clin Transl Oncol, 2014, 16(1):44-48.
25. Wang TS, Cheung K, Farrokhyar F, et al. A meta-analysis of the effect of prophylactic central compartment neck dissection on locoregional recurrence rates in patients with papillary thyroid cancer[J]. Ann Surg Oncol, 2013, 20(11):3477-3483.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Correlation Between BRAF^V600E Gene Mutation and The Prognostic Factors in Papillary Thyroid Microcarcinoma

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Correlation Between BRAFV600E Gene Mutation and The Prognostic Factors in Papillary Thyroid Microcarcinoma

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Correlation Between BRAF^V600E Gene Mutation and The Prognostic Factors in Papillary Thyroid Microcarcinoma