Upregulation of miR-200c and miR-429 Suggests Reversal Towards Epithelial State in Venous Tumour Thrombus of Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma (RCC) has a well-established propensity to form grossly visible tumour thrombi; however a comprehensive understanding of the underlying mechanisms is still lacking. The epithelial-mesenchymal transition (EMT) has been implicated in the progression of many carcinomas, including RCC; however, its exact role in the formation of venous tumour thrombi remains unclear. This study aims to explore the involvement of the EMT in venous invasion in RCC. In 14 patients with WHO/ISUP grade 2/3 clear cell RCC with venous invasion, the expression of main EMT markers (the miR-200 family, miR-205, SNAI1/2, TWIST1, ZEB2, and CDH1) was analyzed by qPCR in the selected tumour regions-the tumour centre (TC), the tumour periphery (TP), the venous tumour thrombus (VTT)-and compared to the corresponding non-neoplastic kidney tissue (N). Expression of E-cadherin, N-cadherin, and ZEB2 was analyzed immunohistochemically. The miR-200 family was downregulated in all areas examined compared to the corresponding N. When comparing the VTT with the TC, upregulation of miR-200c and miR-429 was observed. CDH1 was downregulated when the TP was compared with N, while SNAI2 was downregulated in all tumour regions. There was a strong correlation between the expression of all members of the miR-200 family. Our results demonstrate the presence of distinct molecular signatures between the selected ccRCC regions. The upregulation of two miRNAs in the VTT compared to the TC and their correlation with CDH1 expression could indicate a reversal of the EMT towards a more epithelial cell state in the VTT.