Azim, Sidra1; Mikhael, Alexandra2; Cannavo, Ariana2; Bena, James3; Elsheikh, Tarik4; Berber, Eren1; Olansky, Leann1; Nasr, Christian1
1 Endocrinology & Metabolism Institute, Cleveland Clinic Foundation – Cleveland, OH, USA
2 Medicine Institute, Cleveland Clinic Foundation – Cleveland, OH, USA
3 Department of Quantitave Health Sciences, Cleveland Clinic Foundation – Cleveland, OH, USA
4 Department of Anatomic Pathology, Cleveland Clinic Foundation – Cleveland, OH, USA
Background: BRAF kinase V600E gene mutation (BRAFVE) is present in 29-83% of papillary thyroid cancer (PTC) cases.1 Previous studies evaluating the association between BRAFVE and tumor aggressiveness have shown inconsistent results, and its role as an independent prognostic marker remains controversial.
Objectives: To evaluate the association between BRAFVE and clinico-pathological characteristics, and determine its prognostic significance in PTC.
Methods: We performed retrospective study of 495 patients who had thyroidectomy for PTC. BRAFVE polymerase chain reaction (PCR) analysis was performed on tumor specimens.
Results: BRAFVE was present in 253/495 (50%) of PTC patients. Compared to BRAFVE(-) tumors, BRAFVE(+) tumors were more likely multifocal (61.5 vs 50%, p=0.01), classical and tall cell variants (64.8 vs 32.6% and 11.1 vs 0.41%, p<0.001), and displayed aggressive features including extra thyroidal extension (39.1 vs 12.8%, p<0.001), vascular and lymphatic invasion (27.3 vs 15.3% and 28.9 vs 14.5%, p<0.001), and central lymph node (LN) metastases (44.4 vs 23.5%, p<0.001). BRAFVE (+) tumors were associated with a higher pTNM stage and higher risk of persistent or recurrent disease (ATA intermediate/high vs low risk <0.001). The 2 groups were not different in response to initial therapy (RTT), 5-year disease free survival (DFS) (90.5% vs 92.8%, p=0.39), or 5-year overall survival (OS) (97.6% vs 93%, p=0.66).
Discussion: Like some previous studies, our study showed that BRAFVE is associated with more aggressive clinico-pathological characteristics;2-4 however we found no differences in RTT, DFS or OS.4,5
Conclusion: BRAFVE is associated with more aggressive clinico-pathological features, but does not seem to offer additional prognostic value.
- Costa AM, Herrero A, Fresno MF, et al. BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2008;68(4):618-634.
- Elisei R, Ugolini C, Viola D, et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: A 15-year median follow-up study. J Clin Endocrinol Metab. 2008;93(10):3943-3949.
- Pelizzo MR, Dobrinja C, Casal Ide E, et al. The role of BRAF(V600E) mutation as poor prognostic factor for the outcome of patients with intrathyroid papillary thyroid carcinoma. Biomed Pharmacother. 2014;68(4):413-417.
- Fraser S, Go C, Aniss A, et al. BRAF mutation is associated with decreased disease-free survival in papillary thyroid cancer. World J Surg. 2016.
- 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.