Akt signalling parameters are different in oncocytomas compared to renal cell carcinoma

Abstract

Renal oncocytomas are assigned as benign tumours, and their detailed molecular mechanism is poorly characterised. Activation of the PKB/Akt pathway is assumed to contribute to the pathogenesis and progression of malignant disease. For oncocytomas, hardly any data are available for Akt signalling parameters. Aim of the present work was to determine the alterations of Akt parameters PTEN, phosphorylated Akt (p-Akt) and p27(Kip1) in oncocytoma to better understand the dedifferentiation of renal tumours. By tissue microarray analysis 15 oncocytoma, 18 clear cell renal cell carcinoma (ccRCC) and the corresponding benign tissue were investigated. Significant expression differences between PTEN, p-Akt and p27(Kip1) were determined by immunohistochemistry using One-way ANOVA with all pairs Tukey-Kramer as post hoc analyses. To investigate Akt parameter interactions in the oncocytoma, linear regression analyses were performed. Expression of all proteins was significantly different between the groups and in all groups the lowest for oncocytoma: PTEN: 32.9±13.0 versus 75.5±8.0 versus 123.7±8.8; p<0.001 for oncocytoma, benign parenchyma and ccRCC and 2.7±1.2 versus 40.8±9.5 versus 143.6±12.2; p<0.001 for p27(Kip1). p-Akt expression was significantly different between oncocytoma and ccRCC (67.3±15.7 vs. 144.0±26.6; p<0.05). All three investigated parameters were the lowest in oncocytoma when compared to ccRCC. Expression of PTEN and p27(Kip1) seems to be exceedingly associated with malignant conditions of ccRCC. These findings might contribute to the understanding of tumorous signalling of the PKB/Akt axis in renal tumours.