1. Molecular and Immunophenotypic Correlates of Metastatic Epithelioid Angiomyolipoma Include Alterations of TP53, RB1, and ATRX
- Author
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McCarthy, Michael R., Nichols, Paige E., Sharma, Vidit, Stanton, Melissa L., Reynolds, Jordan P., Pitel, Beth A., Halling, Kevin C., Lohse, Christine M., Herrera-Hernandez, Loren, Thompson, R. Houston, Leibovich, Bradley C., Jimenez, Rafael E., Boorjian, Stephen A., Cheville, John C., and Gupta, Sounak
- Subjects
Gene mutations -- Health aspects ,Tumor proteins -- Analysis ,Immunohistochemistry -- Analysis ,Metastasis -- Risk factors -- Prevention ,Nephrectomy -- Patient outcomes ,Health - Abstract
* Context.--Epithelioid angiomyolipomas (eAMLs) are rare tumors of the kidney that occur in patients with tuberous sclerosis complex or in a sporadic setting; a subset of these tumors exhibit metastatic behavior. Objective.--To analyze molecular profiling data to identify pathogenic alterations in rare cases of metastatic eAML, and to identify immunohistochemistry (IHC)-based surrogate markers. Design.--Molecular profiling data from the American Association for Cancer Research GENIE registry was accessed for 23 patients with angiomyolipomas, and 9 of 16 patients with eAMLs in our institutional registry were evaluated with next-generation sequencing. IHC was performed to screen for alterations of P53, RB, and ATRX for all 16 institutional cases. Results.--Combined alterations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1) were identified using next-generation sequencing in 7 of 8 (88%) patients with metastatic disease compared to a single patient with nonmetastatic disease (RB1 variant of uncertain significance; 1 of 24, 4%). No cases with abnormal IHC results were identified in 11 patients with nonmetastatic disease compared to 3 of 5 patients with metastatic disease. Conclusions.--Our results show that the majority of metastatic eAMLs have mutations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1), while these are rare in patients with nonmetastatic disease. Furthermore, IHC for P53, RB, and ATRX may serve as a screen for a subset of these alterations in resource-limited settings. These findings, if validated in larger data sets, have the potential to predict metastatic behavior in eAMLs. (Arch Pathol Lab Med. 2023;147:817-825; doi: 10.5858/ arpa.2022-0127-OA), Renal angiomyolipomas (AMLs) are mesenchymal neoplasms that are typically comprised of spindle cells arising from thick-walled vessels, intermixed with variable amounts of adipose tissue; they frequently express markers such as [...]
- Published
- 2023