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The status of BRAFV600E mutation among Egyptian patients with papillary thyroid carcinoma

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Abstract

The T1799A activating point mutation in v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) is considered to be the most common genetic change in papillary thyroid cancer. It causes a change in the amino acid valine at position 600 to glutamic acid in the BRAF protein kinase, causing abnormal activation of the signaling pathway mitogen-activated protein kinase. Being associated with aggressive clinicopathological outcomes, it is now considered as a strong prognostic molecular marker for poorer prognosis of papillary thyroid carcinoma. The aim of the study was to investigate the frequency of the BRAFV600E mutation among the Egyptian patients with papillary thyroid carcinoma and to correlate with the clinicopathological status of the patients. The study included 50 formalin-fixed paraffin-embedded thyroid tumor tissue samples collected from the Department of Surgical Pathology, Faculty of Medicine, Cairo University, and the Egyptian National Cancer Institute. Patients’ data archived from records included age, sex, multifocality, lymph node metastasis, vascular invasion, and distant metastasis. The V600E mutation was tested by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. One (2 %) out of the 50 tumor tissue samples was found to be positive for the BRAFV600E mutation. Large-scale studies and inclusion of multiple molecular markers are recommended to elucidate the molecular basis of papillary thyroid carcinoma among Egyptian patients.

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References

  • Albores-Saavedra J, Henson DE, Glazer E, Schwartz AM (2007) Changing patterns in the incidence and survival of thyroid cancer with follicular phenotype-papillary, follicular, and anaplastic: a morphological and epidemiological study. Endocr Pathol 18:1–7

    Article  PubMed  Google Scholar 

  • Basolo F, Torregrossa L, Giannini R, Miccoli M, Lupi C, Sensi E, Berti P, Elisei R, Vitti P, Baggiani A, Miccoli P (2010) Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases. J Clin Endocrinol Metab 95:4197–4205

    Article  CAS  PubMed  Google Scholar 

  • Cantwell-Dorris ER, O’Leary JJ, Sheils OM (2011) BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther 10:385–394

    Article  CAS  PubMed  Google Scholar 

  • Dal Maso L, Bosetti C, La Vecchia C, Franceschi S (2009) Risk factors for thyroid cancer: an epidemiological review focused on nutritional factors. Cancer Causes Control 20(1):75–86

    Article  PubMed  Google Scholar 

  • Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295:2164–2167

    Article  CAS  PubMed  Google Scholar 

  • DeLellis RA, Williams ED (2004) Thyroid and parathyroid tumors: introduction. In: Delellis RA, Lloyd RV, Heitz PU, Eng C (eds) World Health Organization classification of tumors, pathology and genetics, tumors of endocrine organs. IARC, Lyon, pp 50–56

    Google Scholar 

  • Durante C, Puxeddu E, Ferretti E, Morisi R, Moretti S, Bruno R, Barbi F, Avenia N, Scipioni A, Verrienti A, Tosi E, Cavaliere A, Gulino A, Filetti S, Russo D (2007) BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism. J Clin Endocrinol Metab 92:2840–2843

    Article  CAS  PubMed  Google Scholar 

  • Feng L, Li M, Zhang QP, Piao ZA, Wang ZH, Lv S (2011) Utility of BRAF protein overexpression in predicting the metastasis potential of papillary thyroid carcinoma. Oncol Lett 2:59–63

    PubMed Central  PubMed  Google Scholar 

  • Fugazzola L, Puxeddu E, Avenia N, Romei C, Cirello V, Cavaliere A, Faviana P, Mannavola D, Moretti S, Rossi S, Sculli M, Bottici V, Beck-Peccoz P, Pacini F, Pinchera A, Santeusanio F, Elisei R (2006) Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocrinol Relat Cancer 13:455–464

    Article  CAS  Google Scholar 

  • Fukushima T, Suzuki S, Mashiko M, Ohtake T, Endo Y, Takebayashi Y, Sekikawa K, Hagiwara K, Takenoshita S (2003) BRAF mutations in papillary carcinomas of the thyroid. Oncogene 22:6455–6457

    Article  CAS  PubMed  Google Scholar 

  • Garnett M, Marais R (2004) Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6:313–319

    Article  CAS  PubMed  Google Scholar 

  • Goutas N, Vlachodimitropoulos D, Bouka M, Lazaris AC, Nasioulas G, Gazouli M (2008) BRAF and K-RAS mutation in a Greek papillary and medullary thyroid carcinoma cohort. Anticancer Res 28:305–308

    PubMed  Google Scholar 

  • Hodgson NC, Button J, Solorzano CC (2004) Thyroid cancer: is the incidence still increasing? Ann Surg Oncol 11:1093–1097

    Article  PubMed  Google Scholar 

  • Hussain F, Iqbal S, Mehmood A, Bazarbashi S, ElHassan T, Chaudhri N (2013) Incidence of thyroid cancer in the Kingdom of Saudi Arabia, 2000-2010. Hematol Oncol Stem Cell Ther 6:58–64

    Article  PubMed  Google Scholar 

  • Ito Y, Yoshida H, Maruo R, Morita S, Takano T, Hirokawa M, Yabuta T, Fukushima M, Inoue H, Tomoda C, Kihara M, Uruno T, Higashiyama T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Miyauchi A (2009) BRAF mutation in papillary thyroid carcinoma in a Japanese population: its lack of correlation with high-risk clinicopathological features and disease-free survival of patients. Endocr J 56:89–97

    Article  CAS  PubMed  Google Scholar 

  • Jin L, Sebo TJ, Nakamura N, Qian X, Oliveira A, Majerus JA, Johnson MR, Lloyd RV (2006) BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid. Diagn Mol Pathol 15:136–143

    Article  CAS  PubMed  Google Scholar 

  • Kim KH, Suh KS, Kang DW, Kang DY (2005) Mutations of the BRAF gene in papillary thyroid carcinoma and in Hashimoto’s thyroiditis. Pathol Int 55:540–545

    Article  CAS  PubMed  Google Scholar 

  • Kim SK, Song KH, Lim SD, Lim YC, Yoo YB, Kim JS, Hwang TS (2009) Clinical and pathological features and the BRAF(V600E) mutation in patients with papillary thyroid carcinoma with and without concurrent Hashimoto thyroiditis. Thyroid 19:137–141

    Article  PubMed  Google Scholar 

  • Kim SW, Lee JI, Kim JW, Ki CS, Oh YL, Choi YL, Shin JH, Kim HK, Jang HW, Chung JH (2010) BRAFV600E mutation analysis in fine-needle aspiration cytology specimens for evaluation of thyroid nodule: a large series in a BRAFV600E-prevalent population. J Clin Endocrinol Metab 95:3693–3700

    Article  CAS  PubMed  Google Scholar 

  • Kim HS, Kim JO, Lee DH, Lee HC, Kim HJ, Kim JH, Jang YS, Lee JM, Kim SY, Kim YS (2011) Factors influencing the detection of the BRAF T1799A mutation in papillary thyroid carcinoma. Oncol Rep 25:1639–1644

    CAS  PubMed  Google Scholar 

  • Kim YS, Kim JS, Bae JS, Park WC (2013) Clinical implication of the BRAF V600E mutation in papillary thyroid carcinoma. World J Surg Oncol 11:99

    Article  PubMed Central  PubMed  Google Scholar 

  • Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA (2003) High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63:1454–1457

    CAS  PubMed  Google Scholar 

  • Lang BH, Cho SM, Lo CU, Law SC, Lam KY (2007) Staging systems for papillary thyroid carcinoma: a study of 2 tertiary referral centers. Ann Surg 246:114–121

    Article  PubMed Central  PubMed  Google Scholar 

  • Lee JH, Lee ES, Kim YS (2007) Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis. Cancer 110:38–46

    Article  PubMed  Google Scholar 

  • Lee JI, Jang HW, Kim SW, Kim JW, Oh YL, Chung JH (2013) BRAFV600E mutation in fine-needle aspiration aspirates: association with poorer prognostic factors in larger papillary thyroid carcinomas. Head Neck 35:548–553

    Article  PubMed  Google Scholar 

  • Lloyd RV, Buehler D, Khanafshar E (2011) Papillary thyroid carcinoma variants. Head Neck Pathol 5:51–56

    Article  PubMed Central  PubMed  Google Scholar 

  • Mazzaferri EL, Kloos RT (2001) Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 86:1447–1463

    Article  CAS  PubMed  Google Scholar 

  • Melck AL, Yip L, Carty SE (2010) The utility of BRAF testing in the management of papillary thyroid cancer. Oncologist 15:1285–1293

    Article  PubMed Central  PubMed  Google Scholar 

  • Mercer KE, Pritchard CA (2003) Raf proteins and cancer: B-Raf is identified as a mutational target. Biochim Biophys Acta 1653:25–40

    CAS  PubMed  Google Scholar 

  • Mitsiades CS, Negri J, McMullan C et al (2007) Targeting BRAFV600E in thyroid carcinoma: therapeutic implications. Mol Cancer Ther 6:1070–1078

    Article  CAS  PubMed  Google Scholar 

  • Mohammadi-Asl J, Larijani B, Khorgami Z, Tavangar SM, Haghpanah V, Mehdipour P (2009) Prevalence of BRAFV600E mutation in Iranian patients with papillary thyroid carcinoma: a single-center study. J App Sci 9:3593

    Article  Google Scholar 

  • Mokhtar N, Gouda I, Adel I (2007) Malignant endocrine system tumors. In: Mokhtar N, Gouda I, Adel I (eds) Cancer Pathology Registry 2003-2004 and time trend analysis. NCI, El Sheraa, Cairo, pp 91–93

    Google Scholar 

  • Nikiforov YE (2011) Molecular diagnostics of thyroid tumors. Arch Pathol Lab Med 135:569–577

    CAS  PubMed  Google Scholar 

  • Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, Janakiraman M, Solit D, Knauf JA, Tuttle RM, Ghossein RA, Fagin JA (2009) Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res 69:4885–4893

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Salim EI, Moore MA, Al-Lawati JA, Al-Sayyad J, Bazawir A, Bener A, Corbex M, El-Saghir N, Habib OS, Maziak W, Mokhtar HC, Seif-Eldrin IA, Sobue T (2009) Cancer epidemiology and control in the Arab world—past, present and future. Asian Pac J Cancer Prev 10(1):3–16

    PubMed  Google Scholar 

  • Shelis O (2005) Molecular classification and biomarker discovery in papillary thyroid carcinoma. Expert Rev Mol Diagn 5:927–946

    Article  Google Scholar 

  • Sherman NC, Button J, Solorzano CC (2004) Thyroid cancer: is the incidence still increasing? Ann Surg Oncol 11:1093–1097

    Article  Google Scholar 

  • Trovisco V, Soares P, Preto A, de Castro IV, Lima J, Castro P, Maximo V, Botelho T, Moreira S, Meireles AM, Magalhaes J, Abrosimov A, Cameselle-Teijeiro J, Sobrinho-Simoes M (2005) Type and prevalence of BRAF mutations are closely associated with papillary thyroid carcinoma histotype and patients’ age but not with tumour aggressiveness. Virchows Arch 446:589–595

    Article  CAS  PubMed  Google Scholar 

  • Xing M (2005) BRAF mutation in thyroid cancer. Endocrinol Relat Cancer 12:245–262

    Article  CAS  Google Scholar 

  • Xing M (2007) BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 28:742–762

    Article  CAS  PubMed  Google Scholar 

  • Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, Carson KA, Vasko V, Larin A, Tallini G, Tolaney S, Holt EH, Hui P, Umbricht CB, Basaria S, Ewertz M, Tufaro AP, Califano JA, Ringel MD, Zeiger MA, Sidransky D, Ladenson PW (2005) BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab 90:6373–6379

    Article  CAS  PubMed  Google Scholar 

  • Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, O’Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Tufano RP, Pai SI, Zeiger MA, Westra WH, Clark DP, Clifton-Bligh R, Sidransky D, Ladenson PW, Sykorova V (2013) Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 309:1493–1501

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zatelli MC, Trasforini G, Leoni S, Frigato G, Buratto M, Tagliati F, Rossi R, Cavazzini L, Roti E, Degli Uberti EC (2009) BRAF V600E mutation analysis increases diagnostic accuracy for papillary thyroid carcinoma in fine-needle aspiration biopsies. Eur J Endocrinol 161:467–473

    Article  CAS  PubMed  Google Scholar 

  • Zheng X, Xia T, Lin L, Gao S, Lee Y, Yu Y, Wei S, Gao M (2012) BRAFV600E status and clinical characteristics in solitary and multiple papillary thyroid carcinoma: experience of 512 cases at a clinical center in China. World J Surg Oncol 10:104

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

Special thanks go to Dr. Abeer Mostafa, Assistant Professor of Molecular Pathology, National Cancer Institute, for her scientific help through the molecular work. The help of Sara Elkhateeb, resident of chemical pathology in specimen and data collection is also acknowledged. This study is supported by Cairo University Research Funds.

Conflict of interest

Authors disclose no conflict of interest.

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Authors and Affiliations

  1. Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Kasr Al Ainy St, Cairo, Egypt, 11562

    Ahmed El Tawil & Dina Mehaney

  2. Department of Pathology, Faculty of Medicine, Cairo University, Kasr Al Ainy St, Cairo, Egypt, 11562

    Shady Anis & Hany Khattab

  3. Department of Pathology, National Cancer Institute, Cairo University, Kornish El-Nile - Fom El-Khaleg, Cairo, Egypt, 11796

    Asmaa Salama

  4. Department of Nuclear Medicine, Faculty of Medicine, Cairo University, Kasr Al Ainy St, Cairo, Egypt, 11562

    Sherif El-Refaei

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  1. Ahmed El Tawil
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  2. Dina Mehaney
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  4. Asmaa Salama
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Correspondence to Dina Mehaney.

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El Tawil, A., Mehaney, D., Anis, S. et al. The status of BRAFV600E mutation among Egyptian patients with papillary thyroid carcinoma. Comp Clin Pathol 24, 715–720 (2015). https://doi.org/10.1007/s00580-014-1968-9

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  • DOI: https://doi.org/10.1007/s00580-014-1968-9

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