Leonardo Pasik

Abstract 12: Serum carbonic anhydrase IX (CAIX) as diagnostic biomarker in clear cell renal cell carcinoma (ccRCC) patients .

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Clinicians face important pitfalls in the treatment of Renal cell carcinoma (RCC), such as absence of symptoms in early stages of the disease, its high metastatic potential and its resistance to conventional therapy. These facts emphasize the requirement of early diagnosis to optimize the chance of cure. ccRCC, the most common histological type of RCC, is considered a cell metabolic disease which develops from the activation of pseudohypoxic pathways. The transmembrane enzyme CAIX, involved in pH homeostasis and expressed in ccRCC tumors, is considered to be one of the best cellular biomarkers of hypoxia. Our aim was to study the role of serum CAIX as diagnostic biomarker of ccRCC, taking into account that serum contains a rich untapped source of disease-specific information. Employing a quantitative ELISA test (RD MW test p<0.001). Then, we analyzed whether already established clinicopathological variables in RCC were associated with serum CAIX levels, finding a remarkable correlation with tumor size (Spearman test p<0.01). Then, we investigated the usefulness of serum CAIX in the follow-up of these patients. Interestingly in 20/30 (66.7%) ccRCC patients values of CAIX decreased after tumor removal (S2 vs S1). We conclude that serum CAIX could be a useful diagnostic biomarker in ccRCC patients. This would be of relevant importance as there is a lack of molecular biomarkers for this pathology. Citation Format: Maria Elena Knott, Myriam Nunez, Maria Natalia Gandur Quiroga, Gaston Boggio, Julieta Grasselli, Guillermo Gueglio, Pedro Rondot Radio, Mariano Brzesinski, Leonardo Pasik, Carla Pulero, Ana Alvarez, Hector Malagrino, Patricio Garcia Marchinena, Alberto Jurado, Elisa Bal de Kier Joffe, Maria Guadalupe Pallotta, Lydia I. Puricelli. Serum carbonic anhydrase IX (CAIX) as diagnostic biomarker in clear cell renal cell carcinoma (ccRCC) patients . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 12. doi:10.1158/1538-7445.AM2013-12

Abstract 431: Circulating fibroblast growth factor 21 (FGF21) as diagnostic and prognostic biomarker in renal cancer

Clear-cell renal cell carcinoma (ccRCC), the most frequent renal parenchyma malignant neoplasm, is considered a cell metabolic disease. The finding of new biomarkers is needed for better sub-classification of renal cell tumors as well as reliable predictors of outcome and therapy response. Fibroblast Growth Factor 21 (FGF21) is a hepatokine that regulates glucose, energy and lipid metabolism during stress-induced pathologies. Despite the beneficial effects of FGF21 in diabetes and obesity; up to date, the clinical implication of FGF21 as a cancer biomarker was not investigated. Our main goal was to evaluate the role of circulating FGF21 as a diagnostic and prognostic biomarker for ccRCC. Initially, we measured the levels of circulating FGF21 in human healthy controls (HC, n = 51) using a quantitative ELISA test (RD FGF21 values were dichotomized into “low” or “high” using 219.57 pg/ml (50th percentile) as cut-off point. No significant association was observed with age, sex, obesity, triglycerides and known risk factors (Chi square test, NS). The prognostic value of FGF21 was analyzed in terms of disease-free survival (DFS) and overall survival (OS). No significant association was found between serum FGF21 levels and 5- years OS. Kaplan-Meier plots of DFS showed that high levels of serum FGF21 were associated with worse prognosis with a borderline significance. However, multivariate analysis showed that FGF21 expression is a significant independent prognostic factor when adding the variables Fuhrman grade and stage (Cox Regression test). We also collected a second serum sample in 30 patients after successful surgery and we observed that the levels of serum FGF21 decreased in 41.4% of ccRCC patients. In addition, we showed that serum FGF21 levels were significantly increased in 14 patients with chromophobe renal cancer respect to HC (MW test: p Citation Format: Maria Elena Knott, Jose Nicolas Minatta, Lucia Roulet, Guillermo Gueglio, Leonardo Pasik, Stella Maris Ranuncolo, Myriam Nunez, Lydia Ines Puricelli, Mariana Silvia De Lorenzo. Circulating fibroblast growth factor 21 (FGF21) as diagnostic and prognostic biomarker in renal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 431.

Abstract 5570: Prognostic biomarkers in patients with clear cell renal cell carcinoma (ccRCC)

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL In Argentina the renal cell carcinoma (RCC) is the 9th cause of death for cancer in males and 13th in women. Clear cell RCC (ccRCC), the most common histological type of RCC, exhibits a wide spectrum of molecular characteristics that are closely associated with the deregulations of metabolic pathways involved in oxygen-, iron-, energy-, or nutrient-sensing. Primary ccRCC comprises a heterogeneous group of entities with variable clinical outcomes, so the understanding of their molecular features has critical importance to define individual metastatic risk. The aim of this study was to determine tumor tissue expression of specific molecules associated with angiogenic pathways triggered by hypoxic conditions (VEGFR1/Flk-1, VEGFR2/Flt-4 and PDGF-A receptor), with the glucose metabolism (Glut-1) or with survival pathways (p53). Antigen expressions were analyzed by immunohistochemistry on formalin fixed paraffin embedded ccRRC tumors [men: n=18, age: Md 55 years (range 46-72); women: n=12, age: 54.5 (49-82)], from patients who underwent a surgical resection as first treatment. The relationships between the expression of the different antigens and the known prognostic factors in ccRCC were analyzed by Chi-square. The Pearson test was used for correlation analysis. The Kaplan-Meier method was used to estimate disease-free survival (DFS). We observed that about 60-70% of ccRCC tumors expressed VEGFR1, VEGFR2 and Glut-1 at membrane level, but only 15% of them showed PDGF-A staining. In addition, 34% of samples expressed p53 at nuclear level. VEGFR1 expression correlated with the expression of the other membrane receptors studied (p<0.05 Pearson test). Interestingly VEGFR2 and PDGF-A immunopositivity on ccRCC tumors could be associated with the presence of metastasis at diagnosis (p<0.05, Chi square test). On the other hand, the expression of membrane VEGFR2 correlated with tumor size (p<0.01 Pearson). No association was observed between the expression of these biomarkers and histological grade, Fuhrman classification or clinical stage. Kaplan-Meier curves and Log rank test showed that no one of the tumor markers studied were associated with DFS; however we observed that those patients who never relapsed were negative for VEGFR2 and Glut1 antigens.In conclusion, we found that some of the studied biomarkers could be associated with some clinical parameters. In particular, VEGFR2 and PDGF-A membrane immunopositivity was associated with metastatic disease. However, the presence of these antigens in ccRCC samples obtained from surgery did not predict disease-free survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5570. doi:1538-7445.AM2012-5570