Regulation of Tumor Vascular Microenvironment by Nestin and Fms-related Tyrosine Kinase 1 (FLT1) and Their Prognostic Significance in Renal Cell Carcinoma.

Abstract

Background & objective: Hypervascularity is a characteristic feature of renal cell carcinoma (RCC) and microvessel density (MVD) predicts tumor metastasis. Nestin is a stem cell marker that is expressed in proliferating endothelial cells and newly formed vessels and Fms-related tyrosine kinase 1 (FLT1) is a proangiogenic factor. This study aimed to evaluate the expression of Nestin and FLT1 in RCC and their prognostic impact.

Methods: This retrospective study included sixty cases of RCC after obtaining ethical approval. Sections were immunohistochemically stained by Nestin and FLT1 then their expressions were compared to different clinicopathological parameters. MVD was evaluated using Nestin and CD34 and compared to the different parameters.

Results: Nestin was expressed mainly in endothelial cells of small vessels in 65% of cases while FLT1 was expressed in tumor and endothelial cells in 73.3% of cases. Their expressions were significantly associated with aggressive tumor parameters including larger tumors, high-grade tumors, wider tumor extension, and advanced stage. Moreover, Nestin expression was significantly associated with metastasis. MVD evaluated by Nestin showed more associations with larger tumors, high-grade tumors, wider tumor extension, advanced stage, and metastasis than MVD measured by CD34. Nestin and FLT1 positivity and high MVD measured by Nestin were significantly associated with short overall survival.

Conclusion: Nestin and FLT1 expressions in RCC may be associated with aggressive tumor features and short patients' overall survival. MVD evaluated by Nestin may be correlated with tumor progression and metastasis. Nestin and FLT1 may be used as prognostic biomarkers in RCC.