Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma correlates with prognosis.
OBJECTIVE
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; chi(2) test) and the presence of synchronous metastases at the time of primary tumor resection (P = 0.014; chi(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.
Bluemke
Karen
K
Clinic of Urology, Martin-Luther University Halle-Wittenberg, Halle/Saale, Germany.
Bilkenroth
Udo
U
Meye
Axel
A
Fuessel
Susanne
S
Lautenschlaeger
Christine
C
Goebel
Steffen
S
Melchior
Andres
A
Heynemann
Hans
H
Fornara
Paolo
P
Taubert
Helge
H
D014408:Biomarkers, Tumor / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000401:mortality / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053538:Keratin-18 / Q000378:metabolism; D053533:Keratin-8 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis
D014408:Biomarkers, Tumor; D053538:Keratin-18; D053533:Keratin-8