Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis

Abstract

ObjectivesTo determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. Material and methodsObservational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables.A bivariate and multivariate descriptive logistical regression analysis was performed, using the presence of metastasis at diagnosis as dependent variable. ResultsThe study identified 13 (26%) VHL mutations related to nuclear grade (P = 0.036). VHL hypermethylation was found in 20% of cases. VHL expression was associated with the presence of mutations (P = 0.013), and the absence of expression was associated with nuclear grade and the presence of metastasis (P<0.05). HIF-1alpha was negative in only 5 cases. Vascular endothelial growth factor (VEGF) was positive in 31 of 47 cases and was associated with Fuhrman nuclear grade, presence of metastasis, and stage (P<0.05). ERK5 expression was increased in 58% of cases and associated with the presence of metastasis and more advanced stages (P<0.05). In the logistic regression analysis, the only variable remaining in the model was VEGF expression (P = 0.014). ConclusionsVEGF has prognostic value in clear cell renal cell carcinoma, and ERK5 may be a new prognostic marker in this type of tumor owing to its relationship with metastasis and more advanced stages.