Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma

Purpose: Approximately one-third of all Renal Cell Carcinoma (RCC) patients undergoing a nephrectomy face metastatic disease. The availability of novel therapeutics for metastatic patients underscores the importance of identifying patients at risk of recurrence or patients responding well to specific therapies. Unlike clear cell RCC (ccRCC), information on biomarkers for the papillary subtype (pRCC) remains limited. In this review, we identified tissue markers that are differentially expressed between subtypes and may be of diagnostic use. In addition, markers with promising prognostic power for ccRCC and/or pRCC are described and their clinical value is discussed. Materials and methods: To identify diagnostic markers that differentiate between pRCC and ccRCC a Pubmed search was performed, limited to original articles published in the English language between 1990 and 2009, using the terms pRCC/papillary RCC/papillary renal cell carcinoma/papillary kidney cancer, biomarker/biomarkers, protein expression, mass spectrometry and immunohistochemistry. Prognostic markers for ccRCC and pRCC were identified using the search terms kidney cancer, renal cell carcinoma, prognostic marker. biomarker and prognosis. Only markers with independent prognostic value in multivariable analysis were included. Results: 25 proteins are differentially expressed between ccRCC and pRCC, reflecting the molecularly distinct nature of these subtypes. 5 of these proteins were externally validated, which shows their diagnostic potential. Whereas 48 biomarkers with independent prognostic power have been identified for ccRCC patients, only CD44. CA9, p53, Ki67 and PCNA have shown prognostic value in multiple studies. Expression of IMP-3 and VEGF-R2 are independent predictors of survival of pRCC patients, although this is shown in single studies. Conclusions: So far 5 validated diagnostic markers are able to differentiate between ccRCC and pRCC. Few independent prognostic markers have been identified for pRCC in single studies, compared to numerous biomarkers identified for the more common ccRCC. Despite the abundance of promising markers for ccRCC. their exact role in clinical decision making still needs to be established through validation studies.