Diagnostic and Prognostic Molecular Markers in Renal Cell Carcinoma

Purpose

We reviewed the contemporary literature on molecular biomarkers in renal cell carcinoma and their prognostic significance.

Materials and Methods

Articles published during 1981 to 2007 in English on renal cell carcinoma were surveyed using the MEDLINE®/PubMed® database. The subject headings included were genetics, biomarkers, prognosis and risk models of renal cell carcinoma. We present a synthesis of currently known renal cell carcinoma biomarkers at various stages of development and their clinical significance, and prognostic nomograms incorporating biomarkers.

Results

The beneficiary role of biomarkers in renal cell carcinoma is challenged by the relatively low prevalence of the disease. Even if a biomarker for renal cell carcinoma had 100% sensitivity and 99.4% specificity, the positive predictive value of the marker in men older than 65 years would be only 10%. Several biomarkers are being investigated in renal cell carcinoma, of which many relate to pathogenic molecular changes that are currently therapeutic targets. Carbonic anhydrase IX is a von Hippel-Lindau mediated enzyme that is expressed in most renal cell carcinoma cases. High (greater than 85%) expression of this marker indicates favorable prognosis and may predict the response to interleukin-2 therapy. B7-H1 expression in renal cell carcinoma cells/lymphocytes may indicate worse survival, possibly through impaired host antitumor immunity. Prognostic nomograms incorporating clinical variables and molecular markers to refine the prediction of treatment outcomes are in active development and await prospective clinical validation.

Conclusions

Several renal cell carcinoma molecular markers appear promising to refine the prognosis and prediction of localized, advanced or metastatic renal cell carcinoma. Currently carbonic anhydrase IX is the best studied and promising marker. Prospective, multicenter clinical validation aimed at the practical clinical usefulness of renal cell carcinoma biomarkers is warranted.

Key Words: kidney, carcinoma, renal cell, tumor markers, biological, prognosis, diagnosis

Abbreviations and Acronyms: AgNOR, argyrophilic nucleolar organizer region, CAIX, carbonic anhydrase IX, CD, cluster designation, ECOG-PS, Eastern Cooperative Oncology Group performance status, HIF, hypoxia inducible factor, iNOS, inducible nitric oxide synthase, Ki-67, proliferative cell nuclear antigen, mTOR, mammalian target of rapamycin, NMP-22, nuclear matrix protein-22, PTEN, phosphatase and tensin homologue, RCC, renal cell carcinoma, STAT, signal transducer and activator of transcription, TATI, tumor associated trypsin inhibitor, TPS, tissue polypeptide specific antigen, TS, thymidylate synthase, VHL, von Hippel-Lindau