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
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
OBJETIVE To evaluate the 18F-FDG PET/CT capacity for the detection of axillary metastases and compare results with sentinel lymph node biopsy (SLNB).MATERIAL AND METHODS: 99 female patients with clinical T1T2N0 breast cancer were included. Patients with recent breast or axillary surgery, T3T4 disease, ductal carcinoma in situ, inflammatory carcinoma, uncontrolled diabetes mellitus and pregnant or lactation patients were excluded. Pre-operative FDG PET-CT was performed 15 days before surgery, SLNB took place with the combined method (radioisotopes and patent blue). Pearson and Spearman correlation test were used to evaluate association of main variables with a significance level (p) of 0.05.RESULTS: Breast PET-CT results: 80 positive PET/CT. Negative PET/ CT in 19 patients (4invasive lobular carcinoma, 7 tumors <7mm) Sensitivity 81%, specificity 100%.97 patients were operated (2 were stage IV with no surgery criteria). We found significant correlation of the FDG tumor uptake (SUV) with tumor size (p< 0.0001), histological grade (p< 0.009), nuclear grade (p<0.001), mitotic grade (p< 0.007) and Ki 67 (p< 0.0001).In all cases the correlation was positive.There was no correlation with hormonal receptors rate.Axillary PET CT results: positive PET/CT in 16 patients (16%). Of this 6 SNLB were negative (FPR= 9%). Specificity 91%, PET /CT were negative in 81 patients (84%), 17 had axillary metastases(5 micrometastases, 2 isolated tumor cells and 2 lobular carcinoma).Sensitivity:37%.FNR=63%. Correlation of histopatological axillary metastases was positive with breast tumor SUV (P<0.0002) and tumor size (p<0.01), but was not significant with histological, nuclear and mitotic grade, Ki 67,hormonal receptor rate and molecular subtype CONCLUSION: 1- PET / CT does not provide benefits for axillary staging in initial stages due to its low spatial resolution (6-8 mm) 2 –A negative axillary by PET/CT does not replace the sentinel node technique. 3 – We can suspect the presence of axillary metastases when there is an intense FDG uptake in the breast tumor. Citation Format: Cristina Noblia, Eugenia Azar, Dolores Mansilla, Amilcar Osorio, Eduardo Armanasco, Diana Montoya, Martin Ipiña, Gaston Berman, Eduardo Gonzalez, Christian Gonzalez, Gabriel Bruno, Patricia Parma, Carla Pulero, Ana Alvarez. Role of 18 FDG PET/CT in axillary staging in early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-16.
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