Glutathione Peroxidases 1 and 3 Immunoscores in Clear Cell Renal Cell Carcinoma: New Insights from a Case-Series Study

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, with a poor prognosis in advanced stages. Although histological tumor grading is an established prognostic parameter, it often fails to capture the biological heterogeneity of RCC. Therefore, identifying novel biomarkers could enhance early diagnosis and improve predictive accuracy. Here, we aimed to test whether immunophenotypes of specific glutathione peroxidase (GPX) family members may have prognostic value in RCC.

We investigated the relationship between GPX1 and GPX3 immunophenotypes and clinicopathological parameters in 32 surgical specimens of clear cell RCC (ccRCC) with nucleolar grade 1–4 (WHO/ISUP grading). We evaluated the GPX1 and GPX3 immunophenotypes and assigned a histological immunoscore for each marker. For analysis, we used Spearman and point-biserial correlation methods.

Our findings indicated a significant positive correlation between GPX1 immunoscore and high nucleolar grade (r = 0.80, p < 0.0001). In contrast, we observed a significant negative correlation between GPX3 immunoscore and high nucleolar grade (r = −0.77, p < 0.0001). We did not find statistically significant correlations between GPX1 expression and age, sex, tumor localization, or tumor size (p > 0.05), nor with capsular infiltration and invasion of the renal pelvis (p > 0.05). However, we did find statistically significant positive correlations between GPX1 expression and invasion of the renal vein (p = 0.038), perirenal fat (p = 0.043), and peripyelic fat (p = 0.015).

Our data demonstrate that GPX1 and GPX3 immunophenotypes could have a prognostic role for ccRCC, particularly in relation to nucleolar grade. This study has limitations because of the small sample size; however, it underscores the necessity for further research in larger, prospective studies. These studies should more thoroughly examine the associations between GPX1 and GPX3 and clinicopathological parameters, and validate them as potential novel prognostic biomarkers.