PREOPERATIVE MOLECULAR STUDY TO GUIDE SURGICAL APPROACH AND PROGNOSIS OF DIFFERENTIATED THYROID CARCINOMA

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 414-436-HPT Axis Biology & Action
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-435
Debora Lucia Seguro Danilovic*1, Erika Urbano Lima1, Regina Barros Domingues2, Simone Elisa Dutenhefner2, Lenine Garcia Brandao2, Rosalinda Yossie Asato Camargo1 and Suemi Marui1
1Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil, 2Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil
The pV600E BRAF mutation is responsible for 30-80% of papillary thyroid carcinoma. Recent meta-analysis associated BRAF mutation with poor prognostic factors(1). Presumably, preoperative diagnosis of BRAF mutation in thyroid nodules would improve accuracy of fine needle aspiration(FNA) biopsy and guide aggressive initial therapy. This study aims to analyze association of BRAF mutation with prognostic factors and determine benefit of prophylactic central neck dissection(CD) in the presence of BRAF mutation. We prospectively recruited 207 patients with FNA diagnosis of indeterminate or suspicious of cancer(Bethesda III-VI). The pV600E BRAF mutation was studied in cytology smears using real time PCR genotyping technique. We analyzed clinical, histological and therapy results according to BRAF mutation(BRAF+ or-) of 94 subjects with final diagnosis of differentiated thyroid carcinoma(DTC). BRAF+ patients without preoperative diagnosis of lymph nodes metastasis were submitted to total or partial thyroidectomy(TT/TP,BRAF+1) or TT and prophylactic CD(BRAF+2). Recurrent or persistent disease included distant metastasis, loco-regional recurrence or suppressed or stimulated serum thyroglobulin >2ng/dL for >1 year of follow-up. Fifty-one percent of patients were BRAF+ and classic papillary carcinoma corresponded to 67% of them. There were no significant differences between BRAF+ or BRAF- in sex, age, FNA diagnosis, tumor size, histological subtype, multifocality, presence of vascular invasion or extrathyroidal extension, extension of surgery, radioiodine therapy and TNM or American Thyroid Association staging(2). Lymph nodes metastasis were diagnosed in 41% BRAF+ and 34% BRAF-(p=0.91). Distant metastasis occurred only in 4 BRAF- patients. During follow-up period of 28.1±9.9months, there was no significant difference in prevalence of recurrent or persistent disease(4.3vs.13%, p=0.16). Among BRAF+ patients, thirty-one subjects were submitted to TT/TP and 9 subjects to TT+CD. Lymph nodes metastasis were present in 3% BRAF+1 and 44% BRAF+2(p=0.006). Similar difference was found in BRAF- patients(7.4vs.50%,p=0.004). No BRAF+1 or BRAF+2 patient had recurrent or persistent disease. In conclusion, the identification of pV600E BRAF mutation in cytology smears improves preoperative diagnosis of DTC, but it was not associated with poor prognostic factors. Despite short period of follow-up, prophylactic central neck dissection did not guarantee better outcome in BRAF+ patients.

(1) Kim TH et al., Cancer 2012; 118:1764. (2)Cooper DS et al., Thyroid 2009; 19:1167

Nothing to Disclose: DLSD, EUL, RBD, SED, LGB, RYAC, SM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant 2012/00164-0 and 2009/07544-0