BRAF Mutation Status Has a Limited Role in Predicting Long-Term Persistence in Papillary Thyroid Carcinoma (PTC)
Ann E Walts, Andy Pao, Shikha Bose. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Papillary thyroid carcinoma (PTC) accounts for >90% of thyroid cancers in the US. Despite treatment, about 25% of these differentiated cancers persist or recur underscoring the need to identify this subset of tumors at presentation and develop effective targeted therapies. BRAF mutation, detected in up to 65% of PTC, has been associated with aggressive tumor behavior but its role as a prognostic indicator in PTC is not clear. This study compares the frequency of BRAF mutation in persistent PTC to that in PTC with negative long-term follow-up.
Design: 38 patients who underwent total thyroidectomy for conventional and/or follicular variant PTC and had been closely followed for >5 years were identified in our tumor registry. 13 of these patients had persistent metastatic PTC (PPTC) and 25 had negative follow-up (no clinical, biochemical, or imaging evidence of tumor; NPTC). Patient demographics and tumor features (size, focality, extrathyroidal extension, regional lymph node status, margin status) were recorded. After slides were reviewed and diagnoses confirmed, macrodissected formalin fixed paraffin embedded sections of each tumor were analyzed for BRAF V600E (1799T>A) mutation using real-time PCR. Presence of BRAF mutation was correlated with tumor follow-up using Fisher's two-tailed test with p<0.05 as significant.
Results: The PPTC group (8 females, 5 males) ranged from 20 to 75 years in age (median 49 yrs) at thyroidectomy with cytologically and/or histologically confirmed metastases 5 to 26 years (median 7.0 yrs) later. The NPTC group (20 females, 5 males) ranged from 24 to 75 years in age (median 39 yrs) at thyroidectomy with 8 to 21 years (median 17 yrs) of negative follow-up. The median tumor size was 2 cm (range 0.8 to 4.5 cm) in the PPTC group and 1.5 cm (range 0.5 to 3.5 cm) in the NPTC group. At thyroidectomy, positive regional lymph nodes and positive resection margins were each more frequently observed in the PPTC than in the NPTC group (p=0.0001 and p=0.0007, respectively). Comparison of the two groups showed no significant difference in tumor focality (uni vs, multi) or in presence of extrathyroidal extension. BRAF mutation was detected in 11 (84.6%) of the PPTC and in 19 (76.0%) of the NPTC; p=0.69.
Conclusions: No significant difference was observed in the frequency of BRAF V600E mutation detected in the PPTC and NPTC groups, suggesting that BRAF mutation has a limited role in predicting long-term perisistence in PTC. Prospective studies are needed to confirm our findings.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 42, Wednesday Afternoon