Abstract |
Rare reports indicate that the frequency of BRAFV600E mutations is high in atypical Spitz nevi. The purpose of this study was to ascertain the utility of the RAF/RAS mutational status as a diagnostic adjunct in lesions with histologic features that deviate from a typical Spitz nevus and, to examine expression of Insulin growth factor binding protein 7 (IGFBP7), a tumor suppressor acting through autocrine/paracrine pathways to inhibit BRAF- MEK-ERK signaling, in the same. Genomic DNA for genotyping was isolated from 6 regular Spitz nevi and 14 atypical spitzoid nevomelanocytic proliferations (including 1 melanoma with spitzoid histomorphology). NRAS1, NRAS2 and KRAS were analyzed, in addition to BRAFV600E. A mutation in BRAFV600E was noted in only one case-that of a regular Spitz nevus. IGFBP7 expression appeared to be maintained in this case, but was absent in 7/17 cases, which included 5 atypical spitzoid nevomelanocytic proliferations. Lack of expression of IGFBP7 in atypical spitzoid nevomelanocytic proliferations with histologically concerning features but BRAF-WT indicates that the evolutionary path in atypical spitzoid nevomelanocytic proliferations is genetically distinct from that of IGFBP7-negative BRAF-positive melanoma. From an oncogenic BRAF perspective, our findings suggest that the majority of 'atypical' spitzoid nevomelanocytic proliferations are probably no different from conventional Spitz nevi.
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Authors | Andrew Emley, Shi Yang, Narendra Wajapeyee, Michael R Green, Meera Mahalingam |
Journal | Journal of cutaneous pathology
(J Cutan Pathol)
Vol. 37
Issue 3
Pg. 344-9
(Mar 2010)
ISSN: 1600-0560 [Electronic] United States |
PMID | 19788444
(Publication Type: Journal Article)
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Chemical References |
- Insulin-Like Growth Factor Binding Proteins
- insulin-like growth factor binding protein-related protein 1
- BRAF protein, human
- Proto-Oncogene Proteins B-raf
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Topics |
- Adolescent
- Adult
- Aged
- Cell Proliferation
- Child
- Child, Preschool
- Diagnosis, Differential
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Immunohistochemistry
- Insulin-Like Growth Factor Binding Proteins
(genetics, metabolism)
- Male
- Melanoma
(genetics, metabolism)
- Middle Aged
- Mutation
- Nevus, Epithelioid and Spindle Cell
(genetics, metabolism)
- Proto-Oncogene Proteins B-raf
(genetics, metabolism)
- Skin Neoplasms
(genetics, metabolism)
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