Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins

STOYANOFF, TANIA ROMINA; RODRIGUEZ, JUAN PABLO; TODARO, JUAN SANTIAGO; ESPADA, J. DIEGO; MELANA COLAVITA, JUAN PABLO; BRANDAN, NORA CRISTINA; TORRES, ADRIANA MÓNICA; AGUIRRE, MARIA VICTORIA

TUMOR BIOLOGY

KARGER

Lugar: Basel; Año: 2016

1010-4283

Clear cell renal cell carcinoma (ccRCC) is the mostcommon subtype of renal carcinomas. There is great interestto know the molecular basis of the tumor biology of ccRCCthat might contribute to a better understanding of the aggressivebiological behavior of this cancer and to identify earlybiomarkers of disease. This study describes the relationshipamong proliferation, survival, and apoptosis with the expressionof key molecules related to tumoral hypoxia (hypoxiainduciblefactor (HIF)-1α, erythropoietin (EPO), vascular endothelialgrowth factor (VEGF)), their receptors (EPO-R,VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stagesof ccRCC. Tissue samples were obtained at the Urology Unitof the J.R. Vidal Hospital (Corrientes, Argentina), from patientswho underwent radical nephrectomy for renal cancerbetween 2011 and 2014. Four experimental groups accordingto pathological stage and nuclear grade were organized: T1G1(n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). Theexpression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, BclxL,and SCD-1 were evaluated by immunohistochemistry,Western blotting, and/or RT-PCR. Apoptosis was assessedby the TUNEL in situ assay, and tumor proliferation was determinedby Ki-67 immunohistochemistry. Data revealed thatHIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 wereoverexpressed in most samples. The T1G1 group showedthe highest EPO levels, approximately 200 % compared withdistal renal tissue. Bcl-xL overexpression was concomitantwith the enhancement of proliferative indexes. SCD-1 expressionincreased 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 amongthese molecules, which would determine tumor progression inearly stages of ccRCC. Our results demonstrate the relationshipamong proliferation, survival, and apoptosis with the expressionof key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their receptors (EPO-R, VEGFR-2), andSCD-1 in early stages of ccRCC.