Research Article

Ultrasound validation of predictive model for central cervical lymph node metastasis in papillary thyroid cancer on BRAF

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research & Education Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Thyroid Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Shanghai Center for Thyroid Disease, Shanghai 200072, PR China

Department of Medical Ultrasound, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, PR China

Search for more papers by this author

Xiao-Long Li

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research & Education Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Thyroid Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Shanghai Center for Thyroid Disease, Shanghai 200072, PR China

Search for more papers by this author

Yi-Feng Zhang

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research & Education Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Thyroid Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Shanghai Center for Thyroid Disease, Shanghai 200072, PR China

Search for more papers by this author

Dan Wang

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research & Education Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Thyroid Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Shanghai Center for Thyroid Disease, Shanghai 200072, PR China

Search for more papers by this author

Qiao Wang

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research & Education Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Thyroid Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Shanghai Center for Thyroid Disease, Shanghai 200072, PR China

Search for more papers by this author

Chong-Ke Zhao

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research & Education Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Thyroid Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Shanghai Center for Thyroid Disease, Shanghai 200072, PR China

Search for more papers by this author

Ming-Xu Li

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research & Education Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Thyroid Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Shanghai Center for Thyroid Disease, Shanghai 200072, PR China

Search for more papers by this author

Qing Wei

Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, PR China

Search for more papers by this author

Guo Ji

Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, PR China

Search for more papers by this author

Hui-Xiong Xu

*Author for correspondence: Tel.: +86 21 66307539;

E-mail Address: xuhuixiong@126.com

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research & Education Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Thyroid Institute, Tongji University School of Medicine, Shanghai 200072, PR China

Shanghai Center for Thyroid Disease, Shanghai 200072, PR China

Search for more papers by this author

Published Online:5 Jun 2020https://doi.org/10.2217/fon-2020-0069

View article

Abstract

Aim: To compare the value of predictive power of the models for central cervical lymph node metastasis (CLNM) in papillary thyroid carcinomas (PTCs). Patients & methods: 220 PTCs were prospectively enrolled into the study with pathological examination. We established a new risk model with univariate and multivariate analyses and receiver-operating characteristic curves were plotted. Z-test was performed to compare the area under two curves and validated the predictive model for central CLNM in PTCs. The comparison of previous and new predictive model was analyzed. Results: Microcalcification, capsule contact or involvement, internal flow and BRAF^V600E mutation were four independent risk factors for PTCs with central CLNMs. The area under the curves for the new and the previous model were 0.948 and 0.934 (p = 0.572), respectively. Conclusion: Two predictive models showed strong consistency in predicting central CLNM in PTCs. The predictive model may be helpful in selecting appropriate treatment method in PTCs.

Keywords:

References

1. Gruber JJ, Colevas AD. Differentiated thyroid cancer: focus on emerging treatments for radioactive iodine-refractory patients. Oncologist 20(2), 113–126 (2015).
MedlineGoogle Scholar
2. Chow S, Law S, Chan J, Au S, Yau S, Lau W. Papillary microcarci-noma of the thyroid: prognostic significance of lymph node metas-tasis and mutlifocality. Cancer 98(1), 31–40 (2003).
MedlineGoogle Scholar
3. Roh JL, Park JY, Park CI. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: pattern of nodal metastasis, morbidity, recurrence, and postoperative levels of serum parathyroid hormone. Ann. Surg. 245(4), 604–610 (2007).
MedlineGoogle Scholar
4. Goropoulos A, Karamoshos K, Christodoulou A et al. Value of the cervical compartments in the surgical treatment of papillary thyroid carcinoma. World J. Surg. 28(12), 1275–1281 (2004).
MedlineGoogle Scholar
5. Moo TA, McGill J, Allendorf J, Lee J, Fahey T 3rd, Zarnegar R. Impact of prophylactic central neck lymph node dissection on early recurrence in papillary thyroid carcinoma. World J. Surg. 34(6), 1187–1191 (2010).
MedlineGoogle Scholar
6. Khokhar MT, Day KM, Sangal RB et al. Preoperative high-resolution ultrasound for the assessment of malignant central compartment lymph nodes in papillary thyroid cancer. Thyroid 25(12), 1351–1354 (2015).
MedlineGoogle Scholar
7. Jin WX, Ye DR, Sun YH et al. Prediction of central lymph node metastasis in papillary thyroid microcarcinoma according to clinicopathologic factors and thyroid nodule sonographic features: a case-control study. Cancer Manag. Res. 10, 3237–3243 (2018).
Medline CASGoogle Scholar
8. Mercer KE, Pritchard CA. Raf proteins and cancer: b-Raf is identified as a mutational target. Biochim. Biophys. Acta 1653(1), 25–40 (2003).
Medline CASGoogle Scholar
9. Jin L, Sebo TJ, Nakamura N et al. BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid. Diagn. Mol. Pathol. 15(3), 136–143 (2006).
Medline CASGoogle Scholar
10. Xing M. BRAF mutation in thyroid cancer. Endocr. Relat. Cancer 12(2), 245–262 (2005).
Medline CASGoogle Scholar
11. Chen J, Li XL, Zhao CK et al. Conventional ultrasound, immunohistochemical factors and BRAFV600E mutation in predicting central cervical lymph node metastasis of papillary thyroid carcinoma. Ultrasound Med. Biol. 44(11), 2296–2306 (2018).
MedlineGoogle Scholar
12. Haugen BR, Alexander EK, Bible KC et al. 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), 1–133 (2016).
MedlineGoogle Scholar
13. So YK, Son YI, Park JY, Baek CH, Jeong HS, Chung MK. Preoperative BRAF mutation has different predictive values for lymph node metastasis according to tumor size. Otolaryngol. Head Neck Surg. 145(3), 422–427 (2011).
MedlineGoogle Scholar
14. Kim SK, Lee JH, Woo JW et al. BRAF V600E mutation: differential impact on central lymph node metastasis by tumor size in papillary thyroid carcinoma. Head Neck 38(Suppl. 1), E1203–E1209 (2016).
MedlineGoogle Scholar
15. Krishnamurthy A, Ramshankar V, Murherkar K et al. Role and relevance of BRAF mutations in risk stratifying patients of papillary thyroid cancers along with a review of literature. Indian J. Cancer 54(1), 372–378 (2017).
Medline CASGoogle Scholar
16. Maksimovic S, Jakovljevic B, Gojkovic Z. Lymph node metastases papillary thyroid carcinoma and their importance in recurrence of disease. Med. Arch. 72(2), 108–111 (2018).
MedlineGoogle Scholar
17. Zhang L, Wei WJ, Ji QH et al. Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients. J. Clin. Endocrinol. Metab. 97(4), 1250–1257 (2012).
Medline CASGoogle Scholar
18. Choi JB, Lee WK, Lee SG et al. Long-term oncologic outcomes of papillary thyroid microcarcinoma according to the presence of clinically apparent lymph node metastasis: a large retrospective analysis of 5,348 patients. Cancer Manag. Res. 10, 2883–2891 (2018).
MedlineGoogle Scholar
19. Wang Y, Guan Q, Xiang J. Nomogram for predicting central lymph node metastasis in papillary thyroid microcarcinoma: a retrospective cohort study of 8668 patients. Int. J. Surg. 98–102 (2018).
MedlineGoogle Scholar
20. Xu JM, Xu XH, Xu HX et al. Prediction of cervical lymph node metastasis in patients with papillary thyroid cancer using combined conventional ultrasound, strain elastography, and acoustic radiation force impulse ARFI elastography. Eur. Radiol. 26(8), 2611–2622 (2016).
MedlineGoogle Scholar
21. Lai XJ, Zhang B, Jiang YX et al. High risk of lateral nodal metastasis in lateral solitary solid papillary thyroid cancer. Ultrasound Med. Biol. 42(1), 75–81 (2016).
MedlineGoogle Scholar
22. Khoo ML, Asa SL, Witterick IJ, Freeman JL. Thyroid calcification and its association with thyroid carcinoma. Head Neck 24(7), 651–655 (2002).
MedlineGoogle Scholar
23. Sun Y, Fang S, Dong H et al. Correlation between osteopontin messenger RNA expression and microcalcification shown on sonography in papillary thyroid carcinoma. J. Ultrasound Med. 30(6), 765–771 (2011).
MedlineGoogle Scholar
24. Shevde LA, Samant RS. Role of osteopontin in the pathophysiology of cancer. Matrix Biol. 37, 131–141 (2014).
Medline CASGoogle Scholar
25. Wang CS, Lin KH, Chen SL, Chan YF, Hsueh S. Overexpression of SPARC gene in human gastric carcinoma and clinic-pathologic significance. Br. J. Cancer 91(11), 1924–1930 (2004).
Medline CASGoogle Scholar
26. Guarino V, Faviana P, Salvatore G et al. Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness. J. Clin. Endocrinol. Metab. 90(9), 5270–5278 (2005).
Medline CASGoogle Scholar
27. Rubaltelli L, Corradin S, Dorigo A et al. Differential diagnosis of benign and malignant thyroid nodules atelastosonography. Ultraschall. Med. 30(2), 175–179 (2009).
Medline CASGoogle Scholar
28. Zhang Q, Liu BJ, Ren WW et al. Association between BRAF V600E mutation and ultrasound features in papillary. Sci. Rep. 7(1), 4899 (2017).
MedlineGoogle Scholar
29. Du J, Bai X, Lu Y et al. Diagnostic efficacy of ultrasonographic characteristics of thyroid carcinoma in predicting cervical lymph node metastasis. Ultrasound Med. Biol. S0301–S5629 (2015).
MedlineGoogle Scholar
30. Kwak JY, Han KH, Yoon JH et al. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology 260(3), 892–899 (2011).
MedlineGoogle Scholar
31. Moon HJ, Kwak JY, Kim MJ, Son EJ, Kim EK. Can vascularity at power Doppler US help predict thyroid malignancy? Radiology 255(1), 260–269 (2010).
MedlineGoogle Scholar
32. Chammas MC, Gerhard R, de Oliveira IR et al. Thyroid nodules: evaluation with power Doppler and duplex Doppler ultrasound. Otolaryngol. Head Neck Surg. 132(6), 874–882 (2005).
MedlineGoogle Scholar
33. Kwak JY, Kim EK, Youk JH et al. Extrathyroid extension of well differentiated papillary thyroid microcarcinoma on US. Thyroid 18(6), 609–614 (2008).
MedlineGoogle Scholar
34. Song YS, Lim JA, Choi H et al. Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients. Cancer 122(9), 1370–1379 (2016).
Medline CASGoogle Scholar
35. Wang Z, Chen JQ, Liu JL, Qin XG. Clinical impact of BRAF mutation on the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta-analysis. Eur. J. Clin. Invest. 46(2), 146–156 (2016).
Medline CASGoogle Scholar
36. Qu HJ, Qu XY, Hu Z et al. The synergic effect of BRAFV600E mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma. Endocr. J. 65(1), 113–120 (2018).
MedlineGoogle Scholar
37. Henke LE, Pfeifer JD, Ma C et al. BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma. Cancer Med. 4(6), 791–799 (2015).
Medline CASGoogle Scholar
38. Feng JW, Yang XH, Wu BQ, Sun DL, Jiang Y, Qu Z. Predictive factors for central lymph node and lateral cervical lymph node metastases in papillary thyroid carcinoma. Clin. Transl. Oncol. 21(11), 1482–1491 (2019).
MedlineGoogle Scholar
39. Liu W, Cheng R, Ma Y et al. Establishment and validation of the scoring system for preoperative prediction of central lymph node metastasis in papillary thyroid carcinoma. Sci. Rep. 8(1), 6962 (2018).
MedlineGoogle Scholar

Vol. 16, No. 22

Metrics

Downloaded 154 times

History

Received 1 February 2020

Accepted 12 May 2020

Published online 5 June 2020

Published in print August 2020

Information

Keywords

Financial & competing interests disclosure

This work was supported in part by National Natural Science Foundation of China (grants 81671695, 81601502 and 81725008), Shanghai Hospital Development Center (grants 16CR3061B and 16CR2032B), the Science and Technology Commission of Shanghai Municipality (grants 14441900900, 16411971100 and 19441903200), Shanghai Municipal Health Commission (grant 2019LJ21) and Fundamental Research Funds for the Central Universities (grants 22120190021 and 22120190137). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

PDF download