Comparative Immunohistochemical Analysis of FAP and c-MET Expression Across Renal Cell Carcinoma Subtypes: Preliminary Results and Potential Theranostic Implications

Background: Renal cell carcinoma (RCC) comprises multiple histopathological subtypes with distinct biological characteristics and clinical behavior. Despite advances in conventional imaging, the detection of small RCC lesions or distant metastases remains challenging and the prognosis of advanced RCC is still poor. Theranostic approaches are promising tools combining diagnostic imaging and targeted radionuclide-based cancer therapy. The identification of suitable molecular targets in tumor tissue is a major focus of current research. Fibroblast activation protein (FAP) and hepatocyte growth factor receptor (c-MET) have been proposed as theranostic targets in several solid cancers, including RCC. However, available data are limited and inconsistent, particularly regarding expression patterns across different RCC subtypes. Methods: In this study, we evaluated the expression patterns of FAP and c-MET immunohistochemically across major RCC subtypes (clear cell RCC [ccRCC], papillary RCC [pRCC], and chromophobe RCC [cpRCC]). Staining intensity was assessed semi-quantitatively and correlated with histological RCC subtypes. Results: FAP expression differed substantially among RCC subtypes, being highest in ccRCC, significantly lower in pRCC, and largely absent in cpRCC. In contrast, c-MET was ubiquitously expressed across all three RCC subtypes but showed a lower specificity for tumor cells. Conclusions: Our results provide a rationale for further evaluating FAP and c-MET as potential theranostic targets across RCC subtypes and establishing a foundation for future RCC-subtype-specific imaging-pathology correlation studies. Validation in larger multicenter cohorts including paired molecular imaging data is required before their clinical translation can be considered.