Study on Expression of BRAF Gene and Invasiveness of Papillary Thyroid Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YUBo-yang ¹ , YANGPan ¹ , MABu-yun ¹ ,  PENGYu-lan ¹ , XIONGSheng-hua ² , ZOUXiu-he ³

1. Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China;
2. Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China;
3. Center of Thyroid Disease Diagnosis and Treatment, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China;

Corresponding author：

PENGYu-lan, Email: yulanpeng@163.com

Keywords：

Papillary thyroid carcinoma; Papillary thyroid microcarcinoma; BRAF gene mutation; Invasiveness of tumor

DOI：

10.7507/1007-9424.20150207

Video：

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Objective To study the expressions of BRAF gene in papillary thyroid microcarcinoma (PTMC) and papillary thyroid carcinoma (PTC) >1 cm in diameter, and the invasiveness of PTMC and PTC. Methods The data of 275 patients with PTC received surgical treatment and with BRAF gene mutation results in West China Hospital of Sichuan University from 2011 September to 2013 September were retrospectively analyzed. According to the size of tumors, the patients were divided into three groups, was the diameter <1 cm group, 1 cm< diameter≤2 cm group, and diameter >2 cm group,respectively. The ratio of BRAF gene mutation, and the degree of risk of extrathyroidal invasion and lymph node metastasis were compared. Results Univariate analysis showed that tumor size was not related with the age, gender, and BRAF gene mutation rate (P>0.05), while the tumor size was related with the extrathyroidal invasion and lymph node metastasis (P<0.05), and the ratio of BRAF gene mutation was related with the extrathyroidal invasion and lymph node metastasis (P<0.05). Multivariate analysis showed that tumor size was associated with extrathyroidal extension (P=0.009) and lymph node metastasis (P=0.000). Conclusions BRAF gene mutation can increase the extrathyroidal invasion and lymph node metastasis risk of PTC, and it is no significantly correlated with tumor size of PTC. The invasiveness of PTC increases with the increased of tumor size, but the PTMC of BRAF gene mutation positive is still require positive treatment.

Citation： YUBo-yang, YANGPan, MABu-yun, PENGYu-lan, XIONGSheng-hua, ZOUXiu-he. Study on Expression of BRAF Gene and Invasiveness of Papillary Thyroid Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(7): 795-798. doi: 10.7507/1007-9424.20150207 Copy

1.	Frattini M, Ferrario C, Bressan P, et al. Alternativemutations of BRAF, RET and NTRK1 are associatedwith similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene, 2004, 23(44):7436-7440.
2.	Hundahl SA, Fleming ID, Fremgen AM, et al. A national cancer data base report on 53 856 cases of thyroid carcinoma treated in the U.S.,1985-1995. Cancer, 1998, 83(12):2638-2648.
3.	Ito Y, Miyauchi A. A therapeutic strategy for incidentally detected papillary microcarcinoma of the thyroid. Nat Clin Pract Endocrinol Metab, 2007, 3(3):240-248.
4.	Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin, 2011, 61(4):212-236.
5.	符国宏. 分化型甲状腺癌预后因素分析. 山东医药,2009, 49(26):69-70.
6.	Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF^V600E mutation and mortality in patients with papillary thyroid cancer. JAMA, 2013, 309 (14):1493-1501.
7.	Tufano RP, Teixeira GV, Bishop J, et al. BRAF Mutation in papillary thyroid cancer and its value in tailoring initial treatment:a systematic review and meta-analysis. Medicine (Baltimore), 2012, 91(5):274-286.
8.	Pakdaman MN, Rochon L, Gologan O, et al. Incidence and histopathological behavior of papillary microcarcinomas:study of 429 cases. Otolaryngol Head Neck Surg, 2008, 139(5):718-722.
9.	Mahar SA, Husain A, Islam N. Fine needle aspiration cytology of thyroid nodule:diagnostic accuracy and pitfalls. J Ayub Med Coll Abbottabad, 2006, 18(4):26-29.
10.	于波洋,于雷,周洁宏. 超声引导下穿刺活检在甲状腺微小癌诊断中的应用. 重庆医学,2013,42(33):4032-4033.
11.	Pacini F. Thyroid microcarcinoma. Best Pract Res Clin Endocrinol Metab, 2012, 26(4):421-429.
12.	Moosa M, Mazzaferri EL. Occult thyroid carcinoma. Cancer, 1997, 10(4):180-188.
13.	李小龙, 高明, 郑向前, 等. 甲状腺乳头状微小癌的临床生物学特性研究. 中国肿瘤临床, 2008, 35(23):1325-1326.
14.	Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid, 2003, 13(4):381-387.
15.	Yu XM, Wan Y, Sippel RS, et al. Should all papillary thyroid microcarcinomas be aggressively treated? An analysis of 18 445 cases. Ann Surg, 2011, 254(4):653-660.
16.	Lim YC, Choi EC, YoonYH, et al. Central lymph node metastases in unilateral erapapillary thyroid microcacinoma. Br J Surg, 2009, 96(3):253-257.
17.	Kim NH, Beak SK, Baik SH, et al. A patient with micropapillary thyroid carcinoma and macronodular lung metastasis:stable disease for eight years without treatment. Thyroid, 2009, 19(3):309-311.
18.	Godbert Y, Henriques-Figueiredo B, Cazeau AL, et al. A papillary thyroid microcarcinoma revealed by a single bone lesion with no poor prognostic factors. Case Reports Endocrinol, 2013, 2013:719304.
19.	Park YJ, Kim YA, Lee YJ, et al. Papillary microcarcinoma in comparison with larger papillary thyroid carcinoma in BRAF^V600E mutation, clinicopathological features, and immunohistochemical findings. Head Neck, 2010, 32(1):38-45.
20.	Ogilvie JB, Patel KN, Heller KS. Impact of the 2009 American Thyroid Association guidelines on the choice of operation for well-differentiated thyroid microcacinomas, Surgery, 2010, 148(6):1222-1226.
21.	Peyssonnaux C, Eychène A. The RAF/MEK/ERK pathway:new concepts of activation. Biol Cell, 2001, 93(1-2):53-62.
22.	孟超, 高洁, 梁军, 等. 甲状腺乳头状癌并BRAF^V600E突变及原癌基因重排蛋白表达与其侵袭性的关系. 中国医学科学院学报, 2013, 35(1):64-68.
23.	易文君, 钟德玝, 邹琼燕, 等. BRAF基因突变与甲状腺乳头状癌的相关性. 中南大学学报:医学版, 2012, 37(4):370-373.
24.	龚艳萍, 龚日祥, 杨敬, 等. 甲状腺乳头状癌BRAF基因突变与临床病理特征间的关系及临床意义. 四川大学学报:医学版, 2013, 44(4):662-665.
25.	Xing M, BRAF mutation in thyroid cancer, Endocr Relat Cancer, 2005, 12(2):245-262.
26.	孙宇, 石铁锋, 于江涛, 等. BRAF^V600E基因突变与甲状腺乳头状微小癌预后影响因素的相关性. 中国普外基础与临床杂志, 2014, 21(10):1226-1227.
27.	张伟, 王南鹏, 高庆军, 等. 甲状腺乳头状癌BRAF^V600E突变与临床病理特征和甲状腺球蛋白的关系. 中国普外基础与临床杂志, 2015, 22(2):200-201.
28.	Kwak JY, Kim EK, Chung WY, et al. Association of BRAF^V600E mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma. Radiology, 2009, 53(3):854-860.

1. Frattini M, Ferrario C, Bressan P, et al. Alternativemutations of BRAF, RET and NTRK1 are associatedwith similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene, 2004, 23(44):7436-7440.
2. Hundahl SA, Fleming ID, Fremgen AM, et al. A national cancer data base report on 53 856 cases of thyroid carcinoma treated in the U.S.,1985-1995. Cancer, 1998, 83(12):2638-2648.
3. Ito Y, Miyauchi A. A therapeutic strategy for incidentally detected papillary microcarcinoma of the thyroid. Nat Clin Pract Endocrinol Metab, 2007, 3(3):240-248.
4. Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin, 2011, 61(4):212-236.
5. 符国宏. 分化型甲状腺癌预后因素分析. 山东医药,2009, 49(26):69-70.
6. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF^V600E mutation and mortality in patients with papillary thyroid cancer. JAMA, 2013, 309 (14):1493-1501.
7. Tufano RP, Teixeira GV, Bishop J, et al. BRAF Mutation in papillary thyroid cancer and its value in tailoring initial treatment:a systematic review and meta-analysis. Medicine (Baltimore), 2012, 91(5):274-286.
8. Pakdaman MN, Rochon L, Gologan O, et al. Incidence and histopathological behavior of papillary microcarcinomas:study of 429 cases. Otolaryngol Head Neck Surg, 2008, 139(5):718-722.
9. Mahar SA, Husain A, Islam N. Fine needle aspiration cytology of thyroid nodule:diagnostic accuracy and pitfalls. J Ayub Med Coll Abbottabad, 2006, 18(4):26-29.
10. 于波洋,于雷,周洁宏. 超声引导下穿刺活检在甲状腺微小癌诊断中的应用. 重庆医学,2013,42(33):4032-4033.
11. Pacini F. Thyroid microcarcinoma. Best Pract Res Clin Endocrinol Metab, 2012, 26(4):421-429.
12. Moosa M, Mazzaferri EL. Occult thyroid carcinoma. Cancer, 1997, 10(4):180-188.
13. 李小龙, 高明, 郑向前, 等. 甲状腺乳头状微小癌的临床生物学特性研究. 中国肿瘤临床, 2008, 35(23):1325-1326.
14. Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid, 2003, 13(4):381-387.
15. Yu XM, Wan Y, Sippel RS, et al. Should all papillary thyroid microcarcinomas be aggressively treated? An analysis of 18 445 cases. Ann Surg, 2011, 254(4):653-660.
16. Lim YC, Choi EC, YoonYH, et al. Central lymph node metastases in unilateral erapapillary thyroid microcacinoma. Br J Surg, 2009, 96(3):253-257.
17. Kim NH, Beak SK, Baik SH, et al. A patient with micropapillary thyroid carcinoma and macronodular lung metastasis:stable disease for eight years without treatment. Thyroid, 2009, 19(3):309-311.
18. Godbert Y, Henriques-Figueiredo B, Cazeau AL, et al. A papillary thyroid microcarcinoma revealed by a single bone lesion with no poor prognostic factors. Case Reports Endocrinol, 2013, 2013:719304.
19. Park YJ, Kim YA, Lee YJ, et al. Papillary microcarcinoma in comparison with larger papillary thyroid carcinoma in BRAF^V600E mutation, clinicopathological features, and immunohistochemical findings. Head Neck, 2010, 32(1):38-45.
20. Ogilvie JB, Patel KN, Heller KS. Impact of the 2009 American Thyroid Association guidelines on the choice of operation for well-differentiated thyroid microcacinomas, Surgery, 2010, 148(6):1222-1226.
21. Peyssonnaux C, Eychène A. The RAF/MEK/ERK pathway:new concepts of activation. Biol Cell, 2001, 93(1-2):53-62.
22. 孟超, 高洁, 梁军, 等. 甲状腺乳头状癌并BRAF^V600E突变及原癌基因重排蛋白表达与其侵袭性的关系. 中国医学科学院学报, 2013, 35(1):64-68.
23. 易文君, 钟德玝, 邹琼燕, 等. BRAF基因突变与甲状腺乳头状癌的相关性. 中南大学学报:医学版, 2012, 37(4):370-373.
24. 龚艳萍, 龚日祥, 杨敬, 等. 甲状腺乳头状癌BRAF基因突变与临床病理特征间的关系及临床意义. 四川大学学报:医学版, 2013, 44(4):662-665.
25. Xing M, BRAF mutation in thyroid cancer, Endocr Relat Cancer, 2005, 12(2):245-262.
26. 孙宇, 石铁锋, 于江涛, 等. BRAF^V600E基因突变与甲状腺乳头状微小癌预后影响因素的相关性. 中国普外基础与临床杂志, 2014, 21(10):1226-1227.
27. 张伟, 王南鹏, 高庆军, 等. 甲状腺乳头状癌BRAF^V600E突变与临床病理特征和甲状腺球蛋白的关系. 中国普外基础与临床杂志, 2015, 22(2):200-201.
28. Kwak JY, Kim EK, Chung WY, et al. Association of BRAF^V600E mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma. Radiology, 2009, 53(3):854-860.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study on Expression of BRAF Gene and Invasiveness of Papillary Thyroid Carcinoma

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