1. ¹Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
2. ²Department of Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands
3. ³Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
4. ⁴Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
5. ⁵Division of Drug Toxicology, Department of Biomedical Analysis, Faculty of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

Correspondence: Judith YMN Engwegen, JYMN Engwegen, PharmD, Department of Pharmacy and Pharmacology, Slotervaart Hospital, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands. E-mail: apjen@slz.nl

Received 20 June 2006; Accepted 10 October 2006.

Abstract

Currently, no suitable biomarker for the early detection or follow-up of renal cell carcinoma (RCC) is available. We aimed to validate previously reported potential serum biomarkers for RCC obtained with Surface Enhanced Laser Desorption Ionisation-Time of Flight Mass Spectrometry (SELDI-TOF MS) in our laboratory using distinct patient populations. Two sets of sera from RCC patients and healthy controls (HC) were gathered from different institutes and analysed according to published procedures. The first set (40 RCC, 32 HC) consisted of mainly presurgery samples from patients with disease stages I–IV. The second set (26 RCC, 27 HC) were mostly sera from patients with stage-IV disease, drawn after nephrectomy. Only the increased expression of the previously found serum amyloid- (SAA) peak cluster could be validated in a similar RCC patient subset in both our populations in two independent analyses. It was seen both in early- and late-stage disease and in pre- and postsurgery samples. These results were also confirmed by ELISA. Other previously identified biomarker candidates (mass-to-charge ratio's (m/z) 3900, 4107, 4153, 5352 and 5987) proved difficult to reproduce upon duplicate analysis. Modification of the analytical protocol for these markers resulted in their detection, but we did not achieve satisfactory classification of patients and controls with these alleged biomarkers in any of our two sample sets. Instead, two new peaks (m/z 4289 and 8151) were identified with better performance (sensitivity and specificity 65–90%) for separating patients from controls in the first sample set. Concluding, only the SAA peak cluster was validated as a robust RCC biomarker candidate, which is present in a specific subset of these patients, regardless of disease stage or nephrectomy status. In addition, two new peaks were seen which might prove useful as biomarkers, provided these are validated in new populations.