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Metastatic risk stratification of clear cell renal cell carcinoma patients based on genomic aberrations
Author(s) -
Grimm Julia,
Zeuschner Philip,
Janssen Martin,
Wagenpfeil Stefan,
Hartmann Arndt,
Stöhr Christine,
Keck Bastian,
Kahlmeyer Andreas,
Stöckle Michael,
Junker Kerstin
Publication year - 2019
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22749
Subject(s) - risk stratification , receiver operating characteristic , renal cell carcinoma , logistic regression , medicine , oncology , proportional hazards model , cohort , fluorescence in situ hybridization , pathology , biology , gene , genetics , chromosome
Prognostic markers for the definition of the individual metastatic risk in renal cell carcinoma are still missing. The aim of our study was to establish a total number of specific aberrations (TNSA) genetic score as a new prognostic test for metastatic risk evaluation. Fluorescence in situ hybridization (FISH) was performed on isolated cell nuclei of 100 ccRCCs (50 M1/50 M0) and 100 FFPE sections (second cohort, 32 M1/68 M0). For each chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1, 20q11.21q13.32) cut‐off values were determined by receiver‐operator curve (ROC)‐curve analysis. TNSA was calculated based on the dichotomized specific CNVs. The prognostic significance of CNVs was proven by Cox and logistic regression. TNSA was the best predictor of metastasis and recurrence free survival in both cohorts. We derived an algorithm for risk stratification by combining TNSA and T‐category, which increased the prognostic accuracy to 87% (specificity = 86%, sensitivity = 88%). This model divides patients into two risk groups with significantly different RFS, CSS, and OS ( P = 3.8×10 −5 , P = 5×10 −6 and P = 3.57×10 −8 respectively). The genetic risk model was superior to Leibovich score and was able to identify patients with metachronous metastatic spread which were incorrectly classified as “low” or “intermediate risk.” We present a new tool for individual risk stratification by combining genetic alterations with clinico‐pathologic parameters. Interphase FISH proves to be a dependable method for prognostic evaluation in primary tumor tissue on isolated cell nuclei as well as on FFPE sections. Especially in organ‐confined tumors the genetic score seems to be an important tool to identify patients at high risk for metastatic disease.