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Updated: Nov 18, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Ziad Bakouny1, David A Braun1, Sachet A Shukla2
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Abstract:
Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC.
Insights
Sarcomatoid and rhabdoid renal cell carcinoma (S/R RCC) are aggressive cancers. These tumors respond well to immune checkpoint inhibitors (ICI) due to distinct molecular and immune features.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Sarcomatoid and rhabdoid renal cell carcinoma (S/R RCC) are aggressive subtypes with poor characterization.
- Immune checkpoint inhibitors (ICI) show promise for S/R RCC, but underlying mechanisms are unclear.
Purpose of the Study:
- To characterize the molecular, clinical, and immunologic features of S/R RCC.
- To understand the basis for S/R RCC responsiveness to ICI.
Main Methods:
- Analysis of multiple clinical trial and real-world S/R RCC cohorts.
- Molecular profiling including mutation analysis and gene expression.
- Assessment of immune infiltrates and PD-L1 expression.
Main Results:
- S/R RCC exhibits unique molecular alterations: BAP1 mutations, CDKN2A deletions, and MYC pathway activation.
- Tumors demonstrate an immune-inflamed phenotype with heightened immune activation and cytotoxic T-cell infiltration.
- Upregulation of antigen presentation machinery and PD-L1 expression observed.
Conclusions:
- Distinct molecular drivers contribute to S/R RCC aggressivity.
- The immune-inflamed microenvironment explains S/R RCC sensitivity to ICI therapy.
- Findings provide insights into S/R RCC biology and treatment strategies.
