CD34 and FSHR Expression to Differentiate Multiple Subtypes of Benign and Malignant Renal Neoplasms

Abstract

BackgroundCurrently, no markers accurately differentiate benign from malignant renal masses. CD34 and FSHR are transmembrane proteins involved in neo-angiogenetic pathways and are differently expressed in several normal and cancerous tissues. However, little evidence exists on their distribution in different renal tumors. We aimed to evaluate their expressions in various renal tumors and adjacent normal tissue.MethodsWe retrieved 810 histological samples from 26 patients who underwent surgery for suspected RCa. In each case a core of 10 × 1 mm was selected perpendicular to the tumor capsule between normal kidney and tumor. Within this core 30 regions of interest (ROI), each measuring 669 μm × 500 μm, were acquired at 20× magnification (n = 2 adjacent normal tissue; n = 2 tumor capsule; n = 26 tumor). The surface area of FSHR and CD34 immunostaining was quantified in each ROI using number of stained pixels. The results were compared between RCa and normal kidney.ResultsImmunostaining was significantly different in normal, tumor capsular, and tumor tissues (both CD34 and FSHR P < 0.0001), with overall highest expression in normal and lowest in tumor tissues, where CD34 and FSHR were differently expressed amongst different tumor subtypes (both P < 0.0001). CD34 and FSHR were more expressed in benign versus malignant (both P < 0.0001) and in chromophobe carcinoma versus oncocytoma tumor tissues (CD34 P = 0.0003; FSHR P < 0.0001). The discriminating ability of FSHR alone for benign versus malignant (AUC 0.805; 95% CI 0.771 to 0.837) and chromophobe carcinoma versus oncocytoma (AUC 0.973; 95% CI 0.939 to 0.991) was high. In both cases FSHR AUC was significantly higher than CD34 (both P < 0.0001) and equivalent to the combination of CD34 and FSHR (both P > 0.9). The correlation amongst levels of staining in tumor tissues and distance from the capsule were overall weak (Spearman coefficient CD34 to 0.0644; FSHR-0.16322).ConclusionCD34 and FSHR are differentially expressed across renal tumor subtypes and between tumor and surrounding tissues. FSHR expression alone may be a useful tool to differentiate benign from malignant tumors and chromophobe carcinoma from oncocytoma.