Beta-Catenin, Fibromatosis, Mutation Analysis
Distinguishing desmoid-type fibromatosis from other soft tissue tumors, when pathological examination is insufficient for diagnosis
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Desmoid-type fibromatosis is a locally invasive soft tissue tumor. The histological diagnosis of desmoid-type fibromatosis is challenging. Mutations in exon 3 of the beta-catenin gene have been identified in 50% to 87% of desmoid-type fibromatosis, including T41A (121 A->G), S45P (133 T->C), and S45F (134 C->T), but not in other soft tissue tumors. Patients harboring beta-catenin mutations may have a higher recurrence rate compared to the patients with wild-type beta-catenin.
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.
Beta-catenin mutations are detected using PCR and pyrosequencing methods. The mutant allele frequencies (%) are used to determine beta-catenin mutation status. Results are reported as positive, negative, or failed. A beta-catenin mutation-positive result supports a diagnosis of desmoid-type fibromatosis, but a negative result does not necessarily rule out a diagnosis of desmoid-type fibromatosis.
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; 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 <40% of the cell population. Tumor cells are routinely enriched by macrodissection to avoid false-negative results.
Clinical diagnosis and/or therapy should not be based solely on this assay. The results should be considered in conjunction with clinical information, histologic evaluation, and/or additional diagnostic tests.
This test is designed to detect mutations in codons 41 and 45 of the beta-catenin (CTNNB1) gene and does not detect mutations in other areas of the gene.
Beta-catenin mutations were tested by PCR and pyrosequencing in 48 formalin-fixed, paraffin-embedded (FFPE) tissues. Results showed that beta-catenin mutations were specifically present in 21/25 desmoid-type fibromatosis tissues (T41A, 71.4%; S45F, 23.8%; S45P; 4.8%), but not in 23 other soft tissue tumors. The pyrosequencing results were confirmed by conventional PCR and direct sequencing in all cases. Using pathological diagnoses as references, beta-catenin mutation test demonstrated the following characteristics: clinical sensitivity (84%), clinical specificity (100%), positive predict value (100%), and negative predict value (85.2%).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Lazar AJ, Tuvin D, Hajibashi S, et al: Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol 2008;173:1518-1527
2. Amary MF, Pauwels P, Meulemans E, et al: Detection of beta-catenin mutations in paraffin-embedded sporadic desmoid-type fibromatosis by mutation-specific restriction enzyme digestion (MSRED): an ancillary diagnostic tool. Am J Surg Pathol 2007;31:1299-1309
3. Domont J, Salas S, Lacroix L, et al: High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management. Br J Cancer 2010;102:1032-1036