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

Abstract

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 (R&D System), the expression of serum CAIX of 30 ccRCC patients and 16 healthy controls was evaluated. Samples from cancer patients were taken before surgery, without any previous treatment (S1), and after tumor removal (S2). ccRCC patients showed significantly elevated values of serum CAIX (Median 75.89 pg/ml, range 30,8-1482,9) respect to the levels observed in healthy controls (23.29, 0.0-79.9). On the basis of the optimal cut-off point of 34,821 pg/ml serum CAIX, 22/30 cancer patients showed high values of CAIX versus only 1/15 healthy controls (p< 0.01, Chi square test). The assay of serum CAIX expression in our population exhibited a sensitivity of 93.8% and a specificity of 73.3%. Besides, we demonstrated that Stage I ccRCC patients showed significantly lower levels of the circulating enzyme (Md, range expressed in pg/ml CAIX: Stage I= 45.3, 30.8-107.9 vs Stage IV=102.9, 36.2-1482.9; 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 Nuñez, Maria Natalia Gandur Quiroga, Gaston Boggio, Julieta Grasselli, Guillermo Gueglio, Pedro Rondot Radío, Mariano Brzesinski, Leonardo Pasik, Carla Pulero, Ana Alvarez, Hector Malagrino, Patricio Garcia Marchiñena, 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