.png)
BRAF V600E Immunoexpression in Papillary Thyroid Carcinoma and Its Association with Prognostic Factors and Histopathologic Variant
Abstract
Aim: to provide additional information regarding the clinicopathological characteristics of Papillary Thyroid Carcinoma (PTC). Methods: Fifty patient with PTC were reviewed to determine prognostic factors such as age, gender, size of tumor and histologic variant. BRAF V600E mutation was detected by immunohistochemical staining and assessed with H score. Result: BRAF V600E mutations were detected in 17 (34%) cases. There were seven cases with extrathyroidal extension (ETE) p 0,04, 11 cases with lymph node metastasis (LNM) p < 0,001, and 8 cases with tall cell variant p 0,047.The cases with positive BRAF V600E mutation had mean age of 44.71 years, and the size of the tumor between 0.1-4cm. Six cases of them are male and 11 female.
Conclusion: There were significant relationships between BRAF V600E mutation with ETE, LNM, and tall cell variant. There was no significant relationship between BRAF V600E mutation, either with age, gender, or size of the tumor. BRAF V600E immunohistochemical examination can be performed as additional investigation for PTC patients.
Keywords
DOI: http://dx.doi.org/10.19166/med.v8i1.3120
Full Text:
PDFReferences
1. Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R. Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epid. 2013;2013: 1-10.
https://doi.org/10.1155/2013/965212
2. Tang K, Lee C. BRAF mutation in papillary thyroid carcinoma: pathogenic role and clinical implications. J Chin Med Assoc. 2010;73: 113-28.
https://doi.org/10.1016/S1726-4901(10)70025-3
3. Badan Registrasi Kanker Perhimpunan Dokter Spesialis Patologi Indonesia. Kanker di Indonesia tahun 2011, Jakarta (Indonesia): Data histopatologik. 2011.
4. DeLellis RA. Lioyd RV. Heitz PU. Eng C. World health organization classification of tumours: Pathology and genetics of tumours of endocrine organs. 2004. p. 57-66.
5. Holmes L, Hossain J, Opara F. Pediatric thyroid carcinoma incidence and temporal trends in the USA(1973-2007): Race or shifting diagnostic paradigm? ISRN Oncol. 2012;2012: 1-10.
https://doi.org/10.5402/2012/906197
6. Koperek O, Kornauth C, Capper D, Berghoff AS, Asari R, Niederle B. Immunohistochemical detection of the BRAF V600E-mutated protein in papillary thyroid carcinoma. Am J Surg Pathol. 2012;36: 844-50.
https://doi.org/10.1097/PAS.0b013e318246b527
7. Sassolas G, Nejjari Z, Ferraro A, Petruci MD, Rousset B, Chazot FB. Oncogenic alterations in papillary thyroid cancers of young patients. Thyr. 2012;22: 17-26.
https://doi.org/10.1089/thy.2011.0215
8. Tufano RP, Teixeira GV, Bishop J, Carson KA, Xing MB. BRAF mutation in papillary thyroid cancer and its value in tailoring iniial treatment: a systematic review and meta-analysis. Medicine. 2012;91: 274-86.
https://doi.org/10.1097/MD.0b013e31826a9c71
9. Xing MB, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013;309: 1493-501.
https://doi.org/10.1001/jama.2013.3190
10. Finkelstein A, Levy GH, Hui P, Prasad A, Virk R, Chhieng DC, et al. Papillary thyroid carcinomas with and without BRAF V600E mutations are morphologically distinct. Histopathol. 2012;60: 1052-9.
https://doi.org/10.1111/j.1365-2559.2011.04149.x
11. Zagzag J, Pollack A, Dultz L, Dhar S, Ogilvic JB, Heller KS, et al. Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma. J Surg. 2013;154: 1199-205.
https://doi.org/10.1016/j.surg.2013.06.020
12. Nakayama H, Yoshida A, Nakamura Y, Hayashi H, Miyagi Y, Wada N, et al. clinical significance of BRAF (V600E) mutation and ki-67 labeling index in papillary thyroid carcinomas. Anticancer Res. 2007;27: 3645-50.
13. Henke LE, Perkins SM, Pfeifer JD, Ma C, Chen Y, DeWees T, et al. BRAF V600E mutational status in pediatric thyroid cancer. Pediatr Blood Cancer. 2014;61: 1168-72.
https://doi.org/10.1002/pbc.24935
14. Asuragen Inc. Molecular Pathogenesis of Thyroid Cancer. 2011. Cited : http://asuragen.com/ClinicalLab/images/PDF/Molecular_pathogenesis_of_Thyroid_Cancer_White_Paper_Asuragen.pdf. 10 Dec 2014.
15. Nikiforov YE, Ohori NP. Papillary carcinoma. In: Nikiforov YE, Biddinger PW, Thompson LD, editors. Diagnostic pathology and molecular genetics of the thyroid. Philadelphia: Lippincott William & Wilkins;2009. p. 160-213.
16. Budwitt-Novotny DA, McCarty KS, Cox Eb. Immunohistochemical analyses of estrogen receptor in endometrial carcinoma using a monoclonal antibody. Cancer Res. 1986;46: 5419-25.
17. Capper D, Preusser M, Habel A, Sahm F, Ackerman U, Schindler G, et al. Assesment of BRAF V600E mutations status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol. 2011;122: 11-9.
https://doi.org/10.1007/s00401-011-0841-z
18. Ghossein RA, Katabi N, Fagin JA. Immunohistochemical detection of mutated BRAF V600E supports the clonal origin of BRAF-induced thyroid cancers along the spectrum of disease progression. J Clin Endocrinol Metab. 2013;98: 1414-21.
https://doi.org/10.1210/jc.2013-1408
19. De Biase D, Cesari V, Visani M, Casadei GP, Cremonini N, Gandolfi G, et al. High-sensitivity BRAF mutation analysis: BRAF V600E is acquired early during tumor development but is heterogenously distributed in a subset of papillary thyroid carcinomas. J Clin Endocrinol Metab. 2014;99: 1530-8.
https://doi.org/10.1210/jc.2013-4389
20. McKelvie PA, Chan F, Yu Y, Waring P, Gresshoff I, Farrel S, et al. The prognostic significance of the BRAF V600E mutation in papillary thyroid carcinoma detected by mutation-specific immunohistochemistry. Pathol. 2013;45: 637-44.
https://doi.org/10.1097/PAT.0000000000000008
21. Kim TH, Park YJ, Lim JA, Ahn HY, Lee EK, Lee YJ, et al. The association of the BRAF V600E mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer. 2012;118: 1764-73.
https://doi.org/10.1002/cncr.26500
22. Mineo R, Constantino A, Frasca F, Sciacca L, Russo S, Vigneri R, et al. Activation of the hepatocyte growth factor (HGF)-Met system in papillary thyroid cancer: biological effects of HGF in thyroid cancer cells depend on Met expression levels. Endocrinol. 2004;145: 4355−65.
https://doi.org/10.1210/en.2003-1762
23. Xing M. BRAF Mutation in Papillary Thyroid Cancer: Pathogenic Role, Molecular Bases, and Clinical Implications. Endocr Rev. 2007: 28: 742-62.
https://doi.org/10.1210/er.2007-0007
24. Nardone HC, Ziober AF, Livolsi VA, Mandel SJ, Baloch ZW, Weber RS, et al. c-Met expression in tall cell variant papillary carcinoma of the thyroid. Cancer. 2003;98: 1386-93.
https://doi.org/10.1002/cncr.11638
25. Palona I, Namba H, Mitsutake N, Starenki D, Podtcheko A, Sedliarou I, et al. BRAF V600E promotes invasiveness of thyroid cancer cells through nuclear factor kappaB activation. Endocrinol. 2006;147: 5699-707.
https://doi.org/10.1210/en.2006-0400
26. Jo YS, Li S, Song JH, Kwon KH, Lee JC, Rha SY, et al. Influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer. J Clin Endocrinol Metab. 2006; 91: 3667-70.
https://doi.org/10.1210/jc.2005-2836
27. Ruco L, Scarpino S. The pathogenetic role of the HGF/c-Met system in papillary carcinoma of the thyroid. Biomed. 2014;2: 263-74.
https://doi.org/10.3390/biomedicines2040263
28. Ivan M, Bond J.A, Prat M, Comoglio PM, Wynford-Thomas D. Activated RAS and RET oncogenes induce over-expression of c-Met (hepatocyte growth factor receptor) in human thyroid epithelial cells. Oncogene. 1997;14: 2417-23.
https://doi.org/10.1038/sj.onc.1201083
29. Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, et al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol. 2006;30: 216-22.
https://doi.org/10.1097/01.pas.0000176432.73455.1b
30. Alonso-Gordoa T, Diez JJ, Duran M, Grande E. Advances in thyroid cancer treatment: latest evidence and clinical potential. Ther Adv Med Oncol. 2015;7: 22-38.
https://doi.org/10.1177/1758834014551936
31. Ali SM, He J, Carson W, Stephens PJ, Fiorillo J, Lipson D, et al. Extended antitumor response of a BRAF V600E papillary thyroid carcinoma to vemurafenib. Case Rep Oncol. 2014.7: 343-8.
https://doi.org/10.1159/000363377
32. Dadu R, Shah K, Busaidy NL, Waguespack SG, Habra MA, Ying AK, et al. Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience. J Clin Endocrinol Metab. 2015;100: E77-81.
https://doi.org/10.1210/jc.2014-2246
33. Lassalle S, Hofman V, Ilie M, Butori C, Bozec A, Santini J, et al. Clinical impact of the detection of BRAF mutations in thyroid pathology: potential usefulness as diagnostic, prognostic and theraupetic applications. Curr Med Chemist. 2010;17: 1-11.
https://doi.org/10.2174/092986710791111189
34. Frasca F, Nucera C, Pellegriti G, Gangemi P, Attard M, Stella M, et al. BRAF V600E mutation and the biology of papillary thyroid cancer. Endocr Relat Cancer. 2008;15: 191-205.
https://doi.org/10.1677/ERC-07-0212
35. Ciampi R, Nikiforov YE. Minireview: RET/PTC rearrangement and BRAF mutations in thyroid tumorigenesis. Endocrinol. 2007;148: 936-41.
https://doi.org/10.1210/en.2006-0921
36. LiVolsi VA. Papillary thyroid carcinoma: an update. Mod Pathol. 2011;24: S1-9.
https://doi.org/10.1038/modpathol.2010.129
37. Rosai J, Carcangui ML, DeLellis RA. Tumors of the thyroid gland. Atlas of tumor pathology, fascicles 5. Washington DC: Armed forces institute of pathology. 1992. p.65-115.
38. Baloch Z, LiVolsi VA. Pathology of the thyroid gland. In: Livolsi VA, Asa S (eds). Endocrine Pathology. Philadelphia: Churchill Livingston. 2002. p. 61-88.
39. Mazzaferri EL. Long-term outcome of patients with differentiated thyroid carcinoma: effect of therapy. Endocr Pract. 2000;6: 469-76.
https://doi.org/10.4158/EP.6.6.469
40. Mazzaferri EL, Massoll N. Management of papillary and follicular (differentiated) thyroid cancer: new paradigms using recombinant human thyrotropin. Endocr Relat Cancer. 2002;9: 227-47.
https://doi.org/10.1677/erc.0.0090227
41. Xhaard C, Rubino C, Cléro E, Maillard S, Ren Y, Borson-Chazot F, Sassolas G, et al. Menstrual and reproductive factors in the risk of differentiated thyroid carcinoma in young women in France: a population-based case-control study. Am J Epidemiol. 2014;180:1007-17.
https://doi.org/10.1093/aje/kwu220
42. Zivaljevic V, Slijepcevic N, Sipetic S, Paunovic I, Diklic A, Zoric G, et al. Risk factor for well-differentiated thyroid cancer in men. Tumori. 2013;99: 458-62.
https://doi.org/10.1177/030089161309900403
43. Jukkola A, Bloigu R, Ebeling T, Salmela P, Blanco G. Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications. Endocr Relat Cancer. 2004;11: 571-9.
https://doi.org/10.1677/erc.1.00826
44. Xu X, Quiros RM, Gattuso P, Ain KB, Prinz RA. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res. 2003; 63: 4561-7.
45. Kim TY, Kim WB, Rhee YS, Song JY, Kim JM, Gong G. The BRAF mutation is useful for prediction of cinical recurrence in low-risk patients with conventional papillary thyroid carcinoma. Clin Endocrinol. 2006;65: 364-8.
https://doi.org/10.1111/j.1365-2265.2006.02605.x
46. Hundahl SA, Cady B, Cunningham MP, Mazzaferri E, McKee RF, Rosai J, et al. Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in united states during 1996. U.S. and German Thyroid Cancer Study Group. An American College of Surgeons Commision on Cancer Patient Care Evaluation Study. Cancer. 2000;89: 202-17.
https://doi.org/10.1002/1097-0142(20000701)89:1<202::AID-CNCR27>3.0.CO;2-A
47. Carcangui ML, Zampi G, Pupi A, et al. Papillary carcinoma of the thyroid: a clinico-pathologic study of 241 cases treated at the University of Florence, Italy. Cancer 1985;55: 805-28.
https://doi.org/10.1002/1097-0142(19850215)55:4<805::AID-CNCR2820550419>3.0.CO;2-Z
48. Ito Y, Miyauchi A. Prognostic factors of papillary and follicular carcinomas in japan based on data of kuma hospital. J Thyr Res. 2012;20: 1-18.
https://doi.org/10.1155/2012/973497
49. Kim KH, Suh KS, Kang DW, Kang DY. Mutations of the BRAF gene in papillary thyroid carcinoma and in hashimoto's thyroiditis. Pathol Int. 2005;55: 540-5.
https://doi.org/10.1111/j.1440-1827.2005.01866.x
50. Jo YS, Li S, Song JH, Kwon KH, Lee JC, Rha SY, et al. influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer. J Clin Endocrinol Metab. 2006;91: 3667-70.
https://doi.org/10.1210/jc.2005-2836
51. Oler G, Camacho CP, Hojaij FC, Michaluart P, Riggins GJ, Cerutti JM. Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis. Clin Cancer Res. 2008;14: 4735-42.
https://doi.org/10.1158/1078-0432.CCR-07-4372
52. Kwak JY, Kim EK, Chung WY, Moon HJ, Kim MJ, Choi JR. Association of BRAF V600E mutation with poor clinical prognostic factors and US features in korean patients with papillary thyroid microcarcinoma. Radiol. 2009; 253: 854-60.
https://doi.org/10.1148/radiol.2533090471
53. Fernandez IJ, Piccin O, Sciascia S, Cavicchi O, Repaci A, Vicennati V, et al. Clinical significance of BRAF mutation in thyroid papillary cancer. Otolaryngol Head Neck Surg. 2013;148: 919-25.
https://doi.org/10.1177/0194599813481942
54. Min SH, Lee C, Jung KC. Correlation of immunohistochemical markers and BRAF mutation status with histological variants of papillary thyroid carcinoma in the korean population. J Korean Med Sci. 2013;28: 534-41
https://doi.org/10.3346/jkms.2013.28.4.534
55. Ghossein R, Livolsi VA. Papillary thyroid carcinoma tall cell variant. Thyroid. 2008;18: 1179-81.
https://doi.org/10.1089/thy.2008.0164
56. Calangiu C, Simionescu C, Stepan A, Parnov M, Cercelaru L. The Assessment of prognostic histopathological parameters depending on histological patterns of papillary thyroid carcinoma. Curr Health Sci J. 2014;40: 37-41.
57. Ilie M, Lassale S, Long-Mira E, Bonnetaud C, Bordone O, Lespinet V, et al. Diagnostic value of immunohistochemistry for the detection of the BRAF V600E mutation in papillary thyoid carcinoma: comparative analysis with three DNA-based assays. Thyroid. 2014;24: 858-66.
https://doi.org/10.1089/thy.2013.0302
58. Nikiforova MN, Kimura ET, Gandhi M, Bidinger PW, Knauf JA, Basolo F, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003; 88: 5399-404.
https://doi.org/10.1210/jc.2003-030838
59. Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab. 2005;90: 6373-9.
https://doi.org/10.1210/jc.2005-0987
60. Lupi C, Giannini R, Ugolini C, Proietti A, Berti P, Minuto M, et al. Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2007; 92: 4085-90.
https://doi.org/10.1210/jc.2007-1179
61. Leboulleux S, Rubino C, Baudin E, Caillou B, Hartl DM, Bidart J, et al. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab. 2005;90: 5723-9.
https://doi.org/10.1210/jc.2005-0285
62. O'Neill CJ, Bullock M, Chou A, Sidhu SB, Delbridge LW, Robinson BG, et al. BRAF(V600E) mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer. Surg. 2010;148: 1139-45.
https://doi.org/10.1016/j.surg.2010.09.005
Refbacks
- There are currently no refbacks.
Copyright (c) 2021 Erna Kristiani, Endang SR Hardjolukito, Agnes S Harahap, Benyamin Makes
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
MEDICINUS is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Copyright © Fakultas Kedokteran | Universitas Pelita Harapan | Lippo Karawaci, Tangerang, Indonesia, 15811 . All rights reserved. p-ISSN 1978-3094 | e-ISSN 2622-6995