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

• Published in: British journal of cancer Vol. 110; no. 10; pp. 2537 - 2543
• Main Authors: Sanjmyatav, J, Matthes, S, Muehr, M, Sava, D, Sternal, M, Wunderlich, H, Gajda, M, Grimm, M-O, Junker, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.05.2014; Nature Publishing Group
• Subjects: 631/1647/2017/1947; 692/699/67/589/1588/1351; 692/700/1750; Adult; Aged; Aged, 80 and over; Area Under Curve; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - surgery; Chromosome Aberrations; Disease-Free Survival; Drug Resistance; Epidemiology; Female; Humans; In Situ Hybridization, Fluorescence; Interphase; Kaplan-Meier Estimate; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Kidney Neoplasms - surgery; Kidneys; Male; Medical prognosis; Medical sciences; Metastasis; Middle Aged; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Metastasis; Neoplasm Staging; Nephrology. Urinary tract diseases; Oncology; Prognosis; Proportional Hazards Models; Regression analysis; Retrospective Studies; Risk Assessment; ROC Curve; Statistical analysis; Surgery; Tumors; Tumors of the urinary system; Urology; Germany; disease progression; genetic markers; clear cell RCC; metastasis; interphase-FISH; Kidney disease; Human; High risk; Urinary system disease; Mesonephroma; Genetic marker; Interphase; Identification; Malignant tumor; Metastasis; Clear cell; Clear cell carcinoma; Cancerology; Kidney cancer; Fluorescence in situ hybridization; Grawitz tumor; Fish; Molecular biology; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.159

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.