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. 2018 Jul 16;2018:6979073.
doi: 10.1155/2018/6979073. eCollection 2018.

MicroRNAs as Urinary Biomarker for Oncocytoma

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Free PMC article

MicroRNAs as Urinary Biomarker for Oncocytoma

Melanie von Brandenstein et al. Dis Markers. .
Free PMC article

Abstract

The identification of benign renal oncocytoma, its differentiation from malignant renal tumors, and their eosinophilic variants are a continuous challenge, influencing preoperative planning and being an unnecessary stress factor for patients. Regressive changes enhance the diagnostic dilemma, making evaluations by frozen sections or by immunohistology (on biopsies) unreliable. MicroRNAs (miRs) have been proposed as novel biomarkers to differentiate renal tumor subtypes. However, their value as a diagnostic biomarker of oncocytoma in urines based on mechanisms known in oncocytomas has not been exploited. We used urines from patients with renal tumors (oncocytoma, renal cell carcinoma: clear cell, papillary, chromophobe) and with other urogenital lesions. miRs were extracted and detected via qRT-PCR, the respective tumors analyzed by immunohistology. We found isocitrate dehydrogenase 2 upregulated in oncocytoma and oncocytic chromophobe carcinoma, indicating an increased Krebs cycle metabolism. Since we had shown that all renal tumors are stimulated by endothelin-1, we analyzed miRs preidentified by microarray after endothelin-1 stimulation of renal epithelial cells. Four miRs are proposed as presurgical urinary biomarkers due to their known regulatory mechanism in oncocytoma: miR-498 (formation of the oncocytoma-specific slice-form of vimentin, Vim3), miR-183 (associated with increased CO2 levels), miR-205, and miR-31 (signaling through downregulation of PKC epsilon, shown previously).

Figures

Figure 1
Figure 1
Presurgical urinary levels of miRs for renal tumor diagnostic. miR-205, miR-31, miR-498, and miR-183 are highly expressed in the urine of oncocytoma patients (∗∗∗p < 0.001), while miR-1826 and miR-143 are unsuitable as oncocytoma marker. Oncocytoma; RCC: clear cell renal cell carcinoma; pap RCC: papillary renal cell carcinoma; chromo RCC: chromophobe renal cell carcinoma; urothelial Ca: urothelial carcinoma.
Figure 2
Figure 2
Levels of miR-183 in the urine of renal tumor patients after tumor resection. Residual miRs in urine detectable, being highly reduced in oncocytoma. Oncocytoma; RCC: clear cell renal cell carcinoma; pap RCC: papillary renal cell carcinoma; chromo RCC: chromophobe renal cell carcinoma; urothelial Ca: urothelial carcinoma.
Figure 3
Figure 3
Immunohistology of isocitrate dehydrogenase (IDH2) expression in different renal tumors. IDH2 is expressed in eosinophilic chromophobe renal cell carcinoma and oncocytoma, not in other renal carcinomas. (a) Normal kidney, (b) RCC: clear cell renal cell carcinoma, (c) eosinophilic RCC, (d) papillary RCC, (e) chromophobe RCC, (f) eosinophilic chromophobe RCC, and (g) oncocytoma.

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