The background of the study. Fine-needle aspiration biopsy usually provides sufficient tissue to distinguish between benign and malignant thyroid nodules on the basis of cytologic evaluation of the biopsy. However, some biopsies are not diagnostic. Some papillary thyroid carcinomas have a mutation in the BRAF gene, which codes for B-Raf kinase, an enzyme in a signaling pathway involved in cell differentiation and growth. In this study the mutation was sought in biopsy specimens.
How the study was done. Biopsies of thyroid nodules and thyroid tissue from 45 patients were analyzed for BRAF mutations by DNA sequencing and a colorimetric test that specifically detected the BRAF mutation.
The results of the study. Among the 40 patients who underwent surgery, 26 had a thyroid nodule with a nondiagnostic biopsy, 10 had a thyroid nodule with a biopsy indicating papillary carcinoma, 3 had a nodule with a biopsy diagnosis of benign nodule, and 1 had no biopsy. The final pathologic diagnosis was papillary carcinoma in 16 patients, follicular carcinoma in 6, benign adenoma or hyperplastic nodule in 17, and metastatic kidney carcinoma in 1. Five patients did not have surgery; the biopsy revealed benign thyroid cells in 4 and was nondiagnostic in 1.
The colorimetric analysis of the biopsy specimens revealed the BRAF mutation in 8 of the 16 papillary carcinomas (50 percent), but in none of the benign nodules, the follicular carcinomas, or the metastatic kidney carcinoma. The result in the nondiagnostic nodule of the patient not operated on was negative. The results of the DNA sequencing analysis were similar, except that the mutation was detected in only six of the papillary carcinomas.
The conclusions of the study. BRAF gene mutations can be detected in biopsy specimens of some papillary carcinomas, but are not found in follicular carcinomas or benign thyroid nodules.
The original article. Xing M, Tufano RP, Tufaro AP, Basaria S, Ewertz M, Rosenbaum E, Byrne PJ, Wang J, Sidransky D, Ladenson PW. Detection of BRAF mutation on fine needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer. J Clin Endocrinol Metab 2004;89:2867-72.