Identification of high-risk patients with clear cell renal cell carcinoma based on interphase-FISH.

BACKGROUND: The aim of this study was to examine the prognostic value of four significant aberrations based on our previous studies by array-CGH to develop a prognostic Fluorescence-in situ-hybridisation (FISH) assay for clear cell renal cell carcinomas (ccRCC). METHODS: Fluorescence-in situ-hybridisation experiments were performed on 100 ccRCCs (52 metastasised out of 48 non-metastasised). The mean/median follow up of patients was 59/54 months. Commercially available FISH probes were used for each critical chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1 and 20q11.21q13.32). The total number of specific aberrations (TNSA) was calculated for each tumour based on the specific genomic alterations. RESULTS: Total number of specific aberrations was the best predictor of metastasis (area under the curve (AUC)=0.814) compared with single aberrations (AUC: 0.619-0.708) and to 11 different combinations of these 4 aberrations in the receiver operating characteristic curve analysis. Total number of specific aberrations, tumour grade and tumour size were independent predictors of metastasis in the multivariate analysis (P<0.001) for the whole cohort as well as for organ-confined tumours. Total number of specific aberrations and grade could also independently predict cancer-specific mortality (CSM). Total number of specific aberrations demonstrated the highest significance in COX proportional hazard models of overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). CONCLUSIONS: We identified TNSA as an independent prognostic factor which is associated with metastasis occurrence, CSM, OS, CSS and PFS in patients with ccRCCs.

[Tumor profiling of renal cell tumors: relevance for diagnostics and therapy]. / Molekulares Tumorprofiling von Nierenzelltumoren: Relevanz für Diagnostik und Therapie.

Molecular biological tumor markers and prognostic parameters are necessary for differential diagnosis, individual prognosis, and therapy in patients with renal cell tumors. By using high throughput technologies, it is possible to characterize tumor samples comprehensively. Based on specific genetic alterations, histopathological subtypes were defined as independent tumor entities. Genetic characteristics can be used for diagnosis of primary tumor samples and also of biopsies. Furthermore, specific molecular patterns of metastatic tumors are known, allowing the determination of the primary tumor's metastatic potential. The specific protein patterns of serum samples of tumor patients were analyzed, and several candidate proteins have been identified. One of these is SAA-1, which is elevated in patients with clear cell renal cell carcinomas (RCC). New therapeutic options are now available for patients with metastatic RCC. Therefore, it is necessary to select the best therapy for each patient and to detect therapy resistance very early. Biomarkers in tumor tissue and serum were found to correlate with therapy response.

[Molecular characterization of metastatic renal cell carcinomas. Differentiation of prognosis and therapy]. / Molekulare Charakterisierung der metastasierten Nierenzellkarzinome. Individuelle Prognosebewertung und Therapiewahl.

Molecular biological tumor markers and prognostic parameters are necessary for differential diagnosis, individual prognosis, and therapy in patients with renal cell tumors. By using high throughput technologies for DNA, RNA, and protein analysis, it is possible to comprehensively characterize tumor samples. We identified specific molecular patterns of metastatic tumors, allowing the determination of metastatic potential of the primary tumor. Different therapeutic options are now available for patients with metastatic renal cell carcinoma. Therefore, it is necessary to select the best therapy for each patient and to detect therapy resistance very early. Biomarkers in tumor tissue and serum were found correlating with therapy response.