Also of concern is the finding that these patients are likely to require additional surgery. "We were the first to show a higher need for reoperation," Dr. Xing noted.
In his 2005 series, 69% of BRAF-positive patients required more aggressive treatment (additional surgery or external radiation), compared with 14% of BRAF-negative patients (J. Clin. Endocrinol. Metab. 2005;90:6373-9).
Other recent studies have shown the same (Surgery 2010;148:1139-46). In a study at the University of Pittsburgh, the investigators determined that preoperative knowledge of BRAF mutation positivity could have productively altered the initial PTC surgical management in 24% of patients (Surgery 2009;146:1215-23).
Testing Biopsy for BRAF Mutation
"If you have the results of BRAF testing preoperatively, they can help with risk stratification and surgical planning," Dr. Xing said.
In a 2010 study, researchers analyzed the utility of BRAF mutation screening of 61 fine-needle aspiration biopsy (FNAB) specimens for predicting aggressive clinicopathological characteristics of PTMC (Ann. Surg. Oncol. 2010;17:3294-300). The BRAF mutation was significantly associated with multifocality, extrathyroidal invasion, lateral lymph-node metastasis (LNM) and advanced tumor stages. In a multivariate analysis, the BRAF mutation carried an odds ratio of 18 for central LNM (P = .01). The authors concluded that BRAF mutation screening of FNAB specimens can be used to predict aggressive clinicopathological characteristics of PTMC, and that lateral neck nodes should be meticulously analyzed for cases of PTMC demonstrating mutated BRAF.
These results were consistent with those of an earlier study in which Dr. Xing and colleagues calculated odds ratios to show the predictive power of BRAF mutations found in FNAB specimens to preoperatively risk-stratify PTC patients (J. Clin. Oncol. 2009;27:2977-82). (See box.) The positive predictive value of BRAF mutation status was 36%, and the negative predictive value was 88%.
In summary, Dr. Xing emphasized that the BRAF mutation plays a critical role in PTC tumorigenesis and aggressiveness and can be used preoperatively to risk-stratify patients and assist the physician in planning treatment. He joked to attendees: "Send your patients to me first, before you treat, to check for the mutation."
Dr. Xing reported receiving royalties as a coholder of a licensed patent on the discovery of BRAF mutation and its clinical characterization in thyroid cancer.