Prognostic and Therapeutic Implications of Alamandine Receptor MrgD Expression in Clear Cell Renal Cell Carcinoma with Development of Metastatic Disease

Figures

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  Figure 1. MrgD expression in advanced clear cell renal cell carcinoma (mccRCC). (a) Hematoxylin-eosin (H&E) staining of the non-tumor part of the nephrectomized kidney shows proximal convoluted tubules with granular eosinophilic cells (arrows) and glomeruli (asterisks) but also distal nephron tubules (arrowheads). (b) MrgD staining of the non-tumor tissue reveals an intense granular cytoplasmic staining of the proximal tubules (arrows) and weak staining of the distal tubules (arrowheads). Notice that glomeruli can be used as internal negative control (asterisk). (c,d) Low-grade ccRCC shows weak MrgD staining, whereas the high-grade tumor (e,f) shows intense staining. Original magnification ×250.

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  Figure 2. Immunohistochemical staining of MrgD in mccRCC tumors based on clinical and pathological variables grouped according to histological grade (a), size (b), local invasion (pT) (c), lymph node (N) (d), distant metastasis (M) (e), and NCCN stage at diagnosis (f). IMDC risk criteria (g) and ECOG performance status (h) were evaluated at the time of initiating TKI-therapy. MrgD staining intensity was grouped as negative and positive. The “%” symbol on the Y-axis of the graph represents the percentage of cases that were MrgD positive or negative. The χ2 test was used for data analysis. N0: No lymph node metastasis; N1: lymph node metastasis; M0: No distant metastasis; M1: synchronous distant metastasis.

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  Figure 3. Immunohistochemical staining of MrgD in mccRCC tumors according to patients’ response to first- and second-line therapies. MrgD expression was significantly higher in mccRCCs treated with TKIs as first-line therapy with unfavorable responses (MASS) but lower in cases treated with mTORC1 inhibitors as second-line therapy. The “%” symbol on the Y-axis of the graph represents the percentage of cases that were MrgD positive or negative. CR: Complete response; PR: partial response; SD: stable disease. MrgD staining intensity was grouped as negative or positive. The χ2 test was used for data analysis.

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  Figure 4. MrgD expression in mccRCC and patients’ survival. Kaplan–Meier curves and log–rank test demonstrated the significant association between MrgD positivity and 10-year overall (a) and disease-free (b) survival. The number of patients at risk is shown at specific time points throughout the follow-up period.