Stage-dependent prognostic impact of molecular signatures in clear cell renal cell carcinoma, "Beyond the Abstract," by Thomas Weber, MD

BERKELEY, CA ( - To date, we are still not able to reliably predict prognosis with biomarkers in patients with ccRCC. Many studies analyzing the prognostic value of biomarkers were conducted, but most results were conflicting. This potentially reflects the non-uniform molecular changes in ccRCC during its evolution. For example, carbonic anhydrase IX is one of the most important predictors of survival in metastasized ccRCC but has no prognostic value in localized disease. Taking this into account, we stratified our analyses of the prognostic biomarkers in organ-confined ccRCC (noninvasive, T1-T2 N0 M0) as well as advanced localized (pT3-4 N0 M0) and metastasized (any T N1-2 M1-2) ccRCC (invasive ccRCC). This stratification, according to the TNM-grading system, helps as a simple and easily reproducible model for ccRCC with different tumor capabilities (e.g., organ-confined ccRCC does not usually invade the surrounding kidney tissue, which is a characteristic of more advanced tumors).

In this study, immunohistochemical staining patterns of VHL, Ki67, p53, p21, nuclear, and cytoplasmic survivin as well as MVD were analyzed to investigate whether they displayed the heterogeneity of ccRCC. We could show that the survival prediction of the expression profiles of the studied biomarkers differed between the categories of organ-confined, locally-advanced, and metastasized ccRCC. Whereas high p53, Ki67 and nuclear survivin expression was associated with poor disease-free survival in advanced, localized and metastasized ccRCC, low p21 expression was associated with inferior outcome in organ-confined ccRCC. This analysis highlights that the evaluation of prognostic factors stratified to ccRCC subgroups helps to enhance their prognostic ability in the context of the varying tumor biology and the molecular evolution of this disease.

We also analyzed the distribution of the staining pattern of the analyzed biomarkers in central and peripheral tumor areas. Even if no marked heterogeneity of any staining was observed in parallel analyzed large sections, significantly more cells in the periphery of the tumor were Ki67-positive than in the center. This probably reflects that the tumor margin represents the "active" site of tumor growth and development.

Written by:
Thomas Weber, MD as part of Beyond the Abstract on This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Department of Oncology and Haematology
Martin-Luther-University Halle-Wittenberg
Ernst-Grube-Str. 40
06120 Halle (Saale)

Stage-dependent prognostic impact of molecular signatures in clear cell renal cell carcinoma - Abstract

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