title: BRAF and Epithelial-Mesenchymal Transition: Lessons From Papillary Thyroid Carcinoma and Primary Cutaneous Melanoma.
abstract: The increased prevalence of BRAF mutations in thyroid carcinoma and primary cutaneous melanoma (PCM) hint that dysregulation of BRAF might contribute to the noted association between PCM and thyroid carcinoma. A recent study evaluating the rate of BRAFV600E mutations among patients who had been diagnosed with primary papillary thyroid carcinoma (PTC) and PCM showed that patients with either PCM or PTC were at an increased risk of developing the other as a second primary malignant neoplasm. Furthermore, the authors noted that samples from patients suffering from both malignancies exhibited a higher rate of incidence of the BRAFV600E mutation, compared with patients not suffering from both malignancies. These studies support the hypothesis that the pathogenesis of these 2 malignancies might share a conserved molecular pattern associated with dysregulation of the BRAF protein. One mechanism through which BRAF might contribute to PCM and thyroid carcinoma progression is through induction of epithelial-mesenchymal transition (EMT). Specifically, the Snail/E-cadherin axis has been demonstrated as a pathway dysregulated by BRAF, leading to EMT in both malignancies. Our analysis focuses on the results of these recent investigations, and through a review of select molecules relevant to EMT, looks to provide a context by which to better understand the relevance and role of stromal-parenchymal signaling and the BRAF mutation in the pathogenesis of PTC and PCM.
authors.affiliation: *University of Florida College of Medicine, Gainesville, FL †Department of Otolaryngology, Tufts Medical center, Boston, MA ‡Dermatopathology Section, Department of Pathology and Laboratory Medicine, VA Consolidated Laboratories, West Roxbury, MA.
authors.forename: Brendon
authors.initials: B
authors.lastname: Mitchell
authors.forename: Jagdish K
authors.initials: JK
authors.lastname: Dhingra
authors.forename: Meera
authors.initials: M
authors.lastname: Mahalingam
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf