1.Expression and Prognostic Value of VEGF, VEGFR1, VEGFR2, VEGFR3, and E-Cadherin in Clear Cell Renal Cell Carcinoma
Mónica Sanz DEL POZO ; Joaquín Gimeno PELEGRÍN ; Nebay Rodríguez MUÑOZ ; Diana Utrilla BERBERANA ; Javier Bascuas HERNANDEZ ; Alejandro López DEL VAL ; Manuel Gomez BARRERA ; Javier Azua ROMEO ; Victoria Capapé POVES ; Ángel Borque FERNANDO ; José Manuel Sánchez ZALABARDO ; Berta Sáez GUTIÉRREZ
Journal of Urologic Oncology 2025;23(2):132-139
Purpose:
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal carcinoma, accounting for 75%–80% of cases. Vascular endothelial growth factor (VEGF), which promotes angiogenesis via its membrane receptors (VEGFRs), and E-cadherin, which decreases in expression during invasion and metastasis, are both implicated in ccRCC pathogenesis. We analyzed the relationship between these proteins and ccRCC lesions to assess their usefulness as prognostic markers.
Materials and Methods:
Renal tumor tissue samples from nephrectomies of 69 patients were analyzed using immunohistochemical techniques to evaluate the expression of the aforementioned proteins. These findings were then compared with established prognostic scales. Statistical analysis was performed using SPSS Statistics ver. 29.0.1.0.
Results:
VEGF intensity was significantly correlated with tumor size (T; p=0.002), stage (p<0.001), and metastasis (M; p=0.049) according to the TNM classification. VEGFR3 expression correlated positively with tumor size (T; p=0.046) and stage (p=0.040). E-cadherin expression correlated negatively with tumor size (p=0.047). In relation to prognostic scales, VEGF expression correlated with the UCLA Integrated Staging System score (p=0.009), while E-cadherin correlated with the stage, size, grade and necrosis (SSIGN) score (p=0.044). For both overall and disease-free survival, significant differences were observed between the moderate (2++) and intense (3+++) VEGFR3 intensity groups (p=0.009 for both).
Conclusion
VEGF may have prognostic value due to its association with tumor size, stage, metastasis, and the UCLA Integrated Staging System score. Similarly, VEGFR3 shows prognostic potential based on its correlations with tumor size, stage, and its relation to overall and disease-free survival. E-cadherin also demonstrates prognostic significance through its association with tumor size and the SSIGN score.
2.Prognostic Implications of Serum Carbonic Anhydrase IX in Clear Cell Renal Cell Carcinoma
Mónica SANZ DEL POZO ; Cristina Plaza ALONSO ; Álvaro Linacero GRACIA ; Ángela Pradilla DIESTE ; Javier Bascuas HERNÁNDEZ ; Victoria Capape POVES ; María Mata ORUS ; Benjamín Gaya SANCHO ; Laura Zaurín PANIAGUA ; Ángel Borque FERNANDO ; José Manuel Sanchez ZALABARDO ; Berta Sáez GUTIÉRREZ
Journal of Urologic Oncology 2025;23(1):54-62
Purpose:
The present study aimed at determining the expression of carbonic anhydrase IX (CAIX) in tissue and serum of patients with clear cell renal cell carcinoma (ccRCC) and its relationship with clinical-pathological parameters; assessing CAIX as a marker of progression and survival; and studying the relationship of CAIX concentration in serum before and after surgical intervention.
Materials and Methods:
Immunohistochemistry was used to assess the expression of CAIX in tumor and adjacent healthy renal tissues. The concentration of CAIX in serum was determined using commercial enzyme-linked immunosorbent assay before and 24 hours after radical nephrectomy in 60 patients diagnosed with ccRCC. SPSS ver. 28.0.1.0 was used for descriptive and inferential statistical analysis and graphics. A significance level of 0.05 was considered for all statistical tests performed.
Results:
CAIX expression was positive in 59 of the 60 samples of tumor renal tissue, and negative in the 60 samples of healthy renal tissues. Median serum CAIX concentration was higher before nephrectomy (178.25 pg/mL) than after it (59.30 pg/mL), with a high correlation between pre-and postsurgical measurements (r=0.891). Significant differences were found in CAIX concentration according to the following variables: TNM, tumor stage, Fuhrman nuclear grade, progression, and death. Serum CAIX concentration before nephrectomy correlated with disease progression and overall survival, with a hazard ratio of 4.849 for CAIX values greater than 169.95 pg/mL.
Conclusion
CAIX expression in tumor renal tissue was specific, but not clinically useful as a prognostic marker. Measurements of CAIX in serum obtained pre- and postsurgical interventions showed good prognostic potential, correlating with clinical-pathological parameters and estimating the risk of progression. Presurgical intervention serum CAIX concentrations higher than 169.95 pg/mL indicated an almost 5-fold increased risk of death.

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