Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; over expression of stearoyl desaturase-1, epo/epo-r system and hypoxia-related proteins

STOYANOFF, TANIA; RODRÍGUEZ, JUAN PABLO; TODARO, JUAN; ESPADA, DIEGO; MELANA COLAVITA, JUAN PABLO; BRANDAN, NORA; TORRES, ADRIANA; AGUIRRE, MARÍA VICTORIA

TUMOR BIOLOGY

KARGER

Lugar: Basel; Año: 2016

1010-4283

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their receptors (EPO-R, VEGFR-2) and SCD-1 in early stages of ccRCC.Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from 24 patients who underwent radical nephrectomy for renal cancer between 2011 and 2014.Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n=6), T2G1 (n=4), T1G2 (n=7), and T2G2 (n=7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-xL and SCD-1 were evaluated by immunohistochemistry, Western blotting and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1 α, EPO, EPO-R, VEGF and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200% compared with distal renal tissue. Bcl-xL over expression was concomitant with the enhancement of proliferative indexes. SCD- 1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their receptors (EPO-R, VEGFR-2) and SCD-1 in early stages of ccRCC.