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PSMA-Expression Is Highly Associated with Histological Subtypes of Renal Cell Carcinoma: Potential Implications for
Vinh Ngoc Bui1, Lena M Unterrainer1, Matthias Brendel1,2
1Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany.
Abstract:
In renal cell carcinoma (RCC), accurate imaging methods are required for treatment planning and response assessment to therapy. In addition, there is an urgent need for new therapeutic options, especially in metastatic RCC. One way to combine diagnostics and therapy in a so-called theranostic approach is the use of radioligands directed against surface antigens. For instance, radioligands against prostate-specific membrane antigen (PSMA) have already been successfully used for diagnosis and radionuclide therapy of metastatic prostate cancer. Recent studies have demonstrated that PSMA is expressed not only in prostate cancer but also in the neovasculature of several solid tumors, which has raised hopes to use PSMA-guided theranostic approaches in other tumor entities, too. However, data on PSMA expression in different histopathological subtypes of RCC are sparse. Because a better understanding of PSMA expression in RCC is critical to assess which patients would benefit most from theranostic approaches using PSMA-targeted ligands, we investigated the expression pattern of PSMA in different subtypes of RCC on protein level. Immunohistochemical staining for PSMA was performed on formalin-fixed, paraffin-embedded archival material of major different histological subtypes of RCC (clear cell RCC (ccRCC)), papillary RCC (pRCC) and chromophobe RCC (cpRCC). The extent and intensity of PSMA staining were scored semi-quantitatively and correlated with the histological RCC subtypes. Group comparisons were calculated with the Kruskal-Wallis test. In all cases, immunoreactivity was detected only in the tumor-associated vessels and not in tumor cells. Staining intensity was the strongest in ccRCC, followed by cpRCC and pRCC. ccRCC showed the most diffuse staining pattern, followed by cpRCC and pRCC. Our results provide a rationale for PSMA-targeted theranostic approaches in ccRCC and cpRCC.
Insights
Prostate-specific membrane antigen (PSMA) is expressed in tumor vasculature, not tumor cells, across renal cell carcinoma (RCC) subtypes. Clear cell RCC (ccRCC) showed the strongest PSMA expression, supporting PSMA-targeted theranostics for ccRCC and chromophobe RCC (cpRCC).
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Accurate imaging and novel therapies are crucial for renal cell carcinoma (RCC), particularly metastatic disease.
- Theranostic approaches, combining diagnostics and therapy via radioligands targeting surface antigens, show promise.
- Prostate-specific membrane antigen (PSMA) is successfully used in prostate cancer theranostics and is found in the neovasculature of various solid tumors.
Purpose of the Study:
- To investigate prostate-specific membrane antigen (PSMA) expression patterns in different histological subtypes of renal cell carcinoma (RCC) at the protein level.
- To determine if PSMA expression in RCC subtypes supports the development of PSMA-targeted theranostic approaches.
- To correlate PSMA expression with histological subtypes of RCC.
Main Methods:
- Immunohistochemical staining for PSMA was performed on archival tissue samples from clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (cpRCC).
- PSMA staining extent and intensity were semi-quantitatively scored and correlated with RCC subtypes.
- Statistical analysis, including the Kruskal-Wallis test, was used for group comparisons.
Main Results:
- Prostate-specific membrane antigen (PSMA) immunoreactivity was exclusively detected in tumor-associated vessels, not in RCC tumor cells, across all subtypes.
- Staining intensity for PSMA was highest in clear cell RCC (ccRCC), followed by chromophobe RCC (cpRCC), and then papillary RCC (pRCC).
- Clear cell RCC (ccRCC) exhibited the most diffuse PSMA staining pattern, followed by cpRCC and pRCC.
Conclusions:
- The study demonstrates that prostate-specific membrane antigen (PSMA) is expressed in the tumor vasculature of renal cell carcinoma (RCC) subtypes.
- The findings provide a strong rationale for exploring PSMA-targeted diagnostic and therapeutic strategies, particularly in clear cell RCC (ccRCC) and chromophobe RCC (cpRCC).
- Further research into PSMA-guided theranostics may offer new treatment avenues for specific RCC patient populations.
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