BRAF Genetic Heterogeneity in Papillary Thyroid Carcinoma and Its Metastasis
Shikha Bose, Andy Pao, Ann E Walts. Cedars-Sinai Medical Center, Los Angeles, CA
Background: BRAF V600E mutation is reported in up to 65% of papillary thyroid carcinomas (PTC). Detection of this mutation is helpful in the cytodiagnosis of indeterminate thyroid nodules and is a possible stratification tool for extent of surgical treatment as well as a potential therapeutic target in PTC. Heterogeneity for BRAF mutation in tumor samples from a patient with PTC can impact management. This pilot study was designed to assess BRAF genetic heterogeneity (GH) within primary PTCs and between paired primary and metastatic lesions.
Design: 38 patients who underwent total thyroidectomy for conventional and/or follicular variant PTC were identified in our database. They included patients with metastases to regional lymph nodes at thyroidectomy and patients with persistent metastases >5 years. Slides were reviewed, diagnoses confirmed, and patient demographics and tumor size were recorded. Formalin fixed paraffin embedded sections of the primary PTCs and their metastases were macrodissected and analyzed for BRAF V600E (1799T>A) mutation using real-time PCR. BRAF GH was assessed in 3 groups of paired tumor samples:
Group A: two separate areas of the primary tumor [28 cases (in 15 cases one of the areas analyzed was ≤0.5 cm in diameter; in the remaining 13 cases both samples were >1.5 cm)]
Group B: primary tumor vs. metastasis at thyroidectomy [16 cases]
Group C: primary tumor vs. metastasis >5 years post-thyroidectomy [9 cases].
Results: The 38 patients (24 females, 14 males) ranged from 16 to 77 years in age (median 45 yrs) at thyroidectomy. The primary tumors ranged from 0.8 to 4.9 cm in diameter (median 2 cm). The persistent metastases analyzed were excised from 5 to 26 years (median 6 yrs) after thyroidectomy. Analysis for the presence of the BRAF mutation yielded discordant results in 1 (3.6%) of the 28 cases in Group A, 0 (0%) of the 16 cases in Group B, and 2 (22.2%) of the 9 cases in Group C. In both of the discordant cases in Group C, the BRAF mutation was detected in the primary but not in the persistent metastasis excised 6 years post-thyroidectomy.
Conclusions: Our findings suggest that
-heterogeneity for BRAF mutation is infrequent within a primary PTC and BRAF mutation status can be reliably determined from analysis of a small biopsy of the tumor,
-BRAF GH is infrequent between a PTC and its concurrent metastasis but might occur more frequently with tumor persistence,
-larger studies are warranted to confirm our findings.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 40, Wednesday Afternoon