RESUMEN
BACKGROUND: BRAF is a member of the RAF kinase family, and it promotes signaling through the RAS-MAP kinase signal transduction cascade. Research has shown that a majority of melanomas and nevi exhibit an activating V600E (T1799A) mutation in BRAF exon 15. Additional studies of BRAF have demonstrated that the T1799A mutation is absent in uveal melanomas and Spitz nevi. METHODS: The ligase detection reaction (LDR) is a sensitive technique that can identify specific DNA mutations occurring at very low frequency within heterogeneous clinical samples, and it has previously been used to analyze mutations in paraffin-embedded tissue specimens. RESULTS: The LDR can readily detect mutations in DNA extracted from non-microdissected paraffin-embedded sections of common nevi, dysplastic nevi, and melanomas. In addition, this method demonstrated the absence of the V600E (T1799A) mutation within Spitz nevi. CONCLUSION: The LDR is a highly sensitive and specific test for detecting mutations in formalin-fixed tissue. The LDR can be easily adapted to detect any mutation associated with a cutaneous disorder. The absence of the BRAF V600E mutation in Spitz's nevi may serve as a molecular signature to distinguish these lesions from common nevi, dysplastic nevi, and some types of malignant melanoma.
Asunto(s)
Análisis Mutacional de ADN/métodos , Ligasas , Melanoma/genética , Mutación , Nevo/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Secuencia de Bases , ADN/genética , Análisis Mutacional de ADN/normas , Síndrome del Nevo Displásico/genética , Ácido Glutámico , Humanos , Melanocitos/patología , Melanoma/patología , Datos de Secuencia Molecular , Nevo/patología , Sensibilidad y Especificidad , Neoplasias Cutáneas/patología , ValinaRESUMEN
PURPOSE: To determine the accuracy and reliability of magnetic resonance (MR) angiography for identification of stenosis and patent distal vessels in patients with peripheral vascular disease. MATERIALS AND METHODS: Two-dimensional time-of-flight MR angiography and conventional arteriography were performed in 22 patients. Four blinded radiologists independently graded multiple anatomic segments. RESULTS: MR angiography allowed detection of more patent vessel segments than did conventional arteriography. For detection of significant stenosis (> 75%), MR angiography had 43%-67% sensitivity and 74%-89% specificity. Discrepancies in detection of significant stenosis occurred in 39 segments for the most accurate reviewer; 27 of these discrepancies were avoidable. CONCLUSION: For detection of significant stenosis, MR angiography has low to moderate sensitivity and specificity; however, observer variability appears to be a major contributing factor to the discrepancies. Greater reviewer experience or techniques for improving reliability may improve the accuracy of MR angiography in peripheral vascular disease.