Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Renal Cell Carcinoma Correlates with Prognosis

Abstract

Purpose: The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood (so-called circulating tumor cells) for renal cell carcinoma patients. Methods: Two hundred thirty-three peripheral blood samples from 154 renal cell carcinoma patients were investigated for the presence of disseminated tumor cells by autoMACS technique and immunocytochemical staining of cytokeratin. The frequency of circulating tumor cells was analyzed statistically for correlation with relevant clinical data. Results: Two kinds of tumor cells were detected: those with expression of cytokeratin 8/18 (CK+) and cells without a detectable cytokeratin expression, which we called large blue-stained cells with a tumorlike morphology. After following the CD45 autoMACS depletion protocol, we identified circulating tumor cells in 96 (41%) of 233 peripheral blood samples, which originated from 81 (53%) of 154 renal cell carcinoma patients.A significant correlation between the detection of circulating tumor cells and positive lymph node status (P < 0.001; χ 2 test) and the presence of synchronous metastases at the time of primary tumor resection (P = 0.014; χ 2 test) was found. In a multivariate Cox's regression hazard model, presence of CK+ circulating tumor cells was significantly correlated with poor overall survival for renal cell carcinoma patients (relative risk, 2.3; P = 0.048). Conclusions:The presence of circulating tumor cells correlated to lymph node status and presence of synchronous metastases in renal cell carcinoma. It is important to evaluate CK+ and blue-stained tumor cells together to determine the role of circulating tumor cells in tumor behavior and disease progression. Detection of CK+ circulating tumor cells in peripheral blood is a significant and independent prognostic factor for renal cell carcinoma. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2190-4)

Molecular Biomarkers in Advanced Renal Cell Carcinoma

“…Moreover, detection of cytokeratin 8/18-expressing CTCs in peripheral blood correlated with poor OS in a study of 154 patients with RCC (P ¼ 0.048; ref. 77). Further studies are required to fully understand the potential of these markers as predictive and prognostic biomarkers in RCC.…”

Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma

“…The spread of neoplastic cells from primary tumor to distant sites is a crucial step in the metastasis process and, thus, the detection of CTCs may provide evidence about disease aggression. Bluemke and colleagues screened the status of CTCs in the blood samples from renal carcinoma patients and revealed that the presence of CTCs correlated with the lymph node status and synchronous metastasis (9). The ability to detect CTCs by analyzing the expression of CA9 as a tumor-specific biomarker in blood samples has previously been reported (10)(11)(12)(13).…”

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

“…B7-H1, a cell surface glycoprotein that participates in T-cell costimulation, is a another marker of interest that was independently correlated with a greater risk for RCC death [59]. Finally, an intriguing study by Bluemke et al [60] correlated the presence of circulating tumor cells and lymph node positivity, distant metastases, and the risk for tumor-related death. Other studies evaluating the significance of circulating endothelial cells and circulating tumor enzymes are under way [61,62].…”