Complementary Diagnostic Value of ZEB1 and CK7 in Renal Oncocytoma and Chromophobe Renal Cell Carcinoma

Renal oncocytoma (RO) is a benign renal epithelial tumor that may closely mimic chromophobe renal cell carcinoma (chRCC), particularly in limited biopsy specimens. In addition, the expanding spectrum of oncocytic renal neoplasms further complicates the differential diagnosis. This study included 251 renal epithelial tumors, of which 250 were included in statistical analyses. The cohort comprised RO, chRCC, papillary RCC, clear cell RCC, collecting duct carcinoma, multilocular cystic renal neoplasm of low malignant potential, and a single case of eosinophilic vacuolated tumor (EVT). Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tissue, and immunohistochemical expression of ZEB1, CK7, CD117, AMACR, CD10, GATA3, SDHB, Cathepsin K, and FH was assessed using H-score analysis. Statistical evaluation included 1-way ANOVA, receiver operating characteristic (ROC) curve analysis, and binary logistic regression. RO demonstrated significantly higher ZEB1 expression compared with all other tumor subtypes ( P <0.001), while ZEB1 expression was absent in chRCC. The single EVT case, excluded from statistical analysis, also showed no ZEB1 expression. In contrast, CK7 expression was highest in chRCC and minimal in RO. ROC analysis demonstrated excellent diagnostic performance for both markers (ZEB1 AUC=0.941; CK7 AUC=0.945), and combined analysis showed strong discriminatory power, with an overall classification accuracy of 95.5%. ZEB1 represents a promising complementary marker in the differential diagnosis of RO and chRCC. In combination with CK7, it provides a simple and practical immunohistochemical approach that may improve diagnostic accuracy, particularly in limited biopsy specimens. Further validation across the expanding spectrum of oncocytic renal neoplasms is warranted.