BRAF Mutation (T1799A) Analysis by PCR and Sequencing, Thyroid
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Papillary thyroid carcinoma (PTC) accounts for approximately 80% of all thyroid cancers. The BRAF gene mutation (T1799A) in exon 15 is the most common genetic alteration in thyroid cancer, occurring in 30% to 70% of sporadic PTC and 10% to 30% of anaplastic thyroid carcinoma, but not in other types of thyroid tumors.(1-3) Fine-needle aspiration (FNA) biopsy with cytological analysis is the best preoperative diagnostic method for thyroid tumors, but 15% to 20% of FNA biopsies yield indeterminate results. Detection of the BRAF mutation (T1799A) can help in the diagnosis of thyroid tumors, especially for indeterminate cases.
Aiding in the diagnosis of papillary thyroid carcinoma or anaplastic thyroid carcinoma in fine-needle aspirate specimens and formalin-fixed, paraffin-embedded tissue
A negative result does not rule-out the presence of a mutation. A positive result supports a diagnosis of papillary thyroid carcinoma (PTC) or anaplastic thyroid carcinoma (ATC), but a negative result does not necessarily rule-out a diagnosis of PTC or ATC.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Reliable results are dependent on adequate specimen collection and processing. This test has been validated on formalin-fixed, paraffin-embedded tissues and cytology fine-needle aspiration specimens stained with Papanicolaou; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause PCR failure. False-negative results may occur in heterozygous tumor specimens when tumor cells comprise <60% of the cell population.Tumor cells are routinely enriched by macrodissection to avoid false-negative results.
Clinical diagnosis and therapy should not be based solely on this assay. The results should be considered in conjunction with clinical information, histologic evaluation, and additional diagnostic tests.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Jin L, Sebo TJ, Nakamura N, et al: BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid. Diagn Mol Pathol 2006;15:136-143
2. Nakamura N, Carney JA, Jin L, et al: RASSF1A and NORE1A methylation and BRAFV600E mutations in thyroid tumors. Lab Invest 2005;85:1065-1075
3. Nikiforova MN, Kimura ET, Gandhi M, et al: BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 2003;88:5399-5404