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Production, Characterization and Potential Uses of a 3D Tissue-engineered Human Esophageal Mucosal Model
Published on: May 18, 2015
Analyses of molecular and histopathologic features and expression of PRAME by immunohistochemistry in mucosal
Aimi Toyama1, Lianne Siegel2, Andrew C Nelson3
1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA. toyama@umn.edu.
Abstract:
Mucosal melanomas are rare, and less is known about the biomarkers of this subtype in comparison to cutaneous or uveal melanomas. Preferentially expressed antigen in melanoma (PRAME) has been studied as a tool for prognostication of uveal melanomas, and immunotherapy against PRAME-expressing tumor cells has already shown promise. Our goal was to retrospectively analyze 29 cases of mucosal melanomas at our institution to determine if any molecular and histopathologic prognosticators could be identified, as well as to study PRAME expression and its association with prognosis. We found that the majority of mucosal melanomas expressed PRAME and a high PRAME expression score predicted a poor prognosis. There was no association between prognosis and the histomorphologic features analyzed, such as presence of spindle cell or epithelioid predominance. BRAF mutations were absent in 16 of 16 cases tested. Pathogenic NRAS mutations were detected in 3 of 11 cases tested and were associated with shorter overall survival compared to those without NRAS alterations, but the presence of NRAS mutations did not correlate with PRAME expression. In conclusion, an increase in PRAME expression and the presence of a pathogenic NRAS were both associated with a worse prognosis in mucosal melanomas.
Insights
Preferentially expressed antigen in melanoma (PRAME) and NRAS mutations are poor prognostic markers in mucosal melanoma. High PRAME expression and NRAS alterations correlate with worse outcomes, guiding future treatment strategies for this rare cancer.
Area of Science:
- Oncology
- Dermatology
- Pathology
Background:
- Mucosal melanomas are rare, with limited understanding of their biomarkers compared to other melanoma types.
- Preferentially expressed antigen in melanoma (PRAME) is a known prognostic factor in uveal melanoma, with therapeutic potential.
Purpose of the Study:
- To identify molecular and histopathologic prognosticators in mucosal melanoma.
- To investigate the expression of PRAME and its correlation with prognosis in mucosal melanoma.
Main Methods:
- Retrospective analysis of 29 mucosal melanoma cases.
- Assessment of PRAME expression, histomorphologic features, and genetic mutations (BRAF, NRAS).
Main Results:
- The majority of mucosal melanomas expressed PRAME, with high expression correlating with a poor prognosis.
- No association was found between prognosis and histomorphologic features.
- BRAF mutations were absent; NRAS mutations were detected in a subset of cases and associated with shorter overall survival.
- NRAS mutations did not correlate with PRAME expression.
Conclusions:
- Increased PRAME expression is a significant indicator of poor prognosis in mucosal melanoma.
- Pathogenic NRAS mutations are associated with worse outcomes in mucosal melanoma.
- Both PRAME expression and NRAS alterations serve as potential prognostic markers for mucosal melanoma.
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