The level of cadherin-6 mRNA in peripheral blood is associated with the site of metastasis and with the subsequent occurrence of metastases in renal cell carcinoma.
BACKGROUND
To evaluate the significance of the presence of circulating renal cell carcinoma (RCC) cells in the development of metastases, the authors extended a previous study to quantify cadherin-6 mRNA levels in association with the pattern of metastasis.


METHODS
Cadherin-6 mRNA levels were measured in peripheral blood samples from 66 patients with RCC, including 55 patients who had newly diagnosed RCC (43 without metastases and 12 with metastases) and 11 patients who had recurrent RCC. For quantitative polymerase chain reaction analysis, a cutoff value was determined in blood samples from 25 healthy volunteers and was verified in samples from 5 healthy controls and from 10 patients who had other malignancies. The correlation between the site of metastases and the cadherin-6 mRNA level was analyzed, and a follow-up study (median, 39 months) to track subsequent metastases was performed after patients underwent nephrectomy.


RESULTS
Cadherin-6 was found in 69.9% of patients with metastases and in 34.9% of patients without apparent metastases (P = 0.0099). In the group of patients with recurrent RCC, patients who had only pulmonary metastases had a significantly lower positivity rate (25.0%) compared with patients who had distant metastases (85.7%; P = 0.044). Among 43 patients with newly diagnosed RCC, 5 of 15 patients who were positive for cadherin-6 had metastases after nephrectomy, whereas only 2 of the 28 patients with negative cadherin-6 status had recurrent disease (P = 0.0398). In addition, the recurrence-free survival of patients who were positive for cadherin-6 was poorer compared with the survival of patients who were negative for cadherin-6 (P = 0.062).


CONCLUSIONS
The quantification of cadherin-6 mRNA in peripheral blood may be a significant predictive marker for current and future metastases. However, subsequent metastases did not always correlate with levels of cadherin-6 mRNA. This may have been due either to the small numbers of circulating tumor cells or to the low levels cadherin-6 mRNA in circulating tumor cells.
Department of Urology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-City, Ibaraki, Japan. torushim@md.tsukuba.ac.jp
Toru
T
Shimazui
Kazuhiro
K
Yoshikawa
Hirotsugu
H
Uemura
Yoshihiko
Y
Hirao
Shinsuke
S
Saga
Hideyuki
H
Akaza
D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000556:secondary*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000473:pathology*; D008297:Male; D009364:Neoplasm Recurrence, Local; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D009392:Nephrectomy; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D014408:Biomarkers, Tumor; D015820:Cadherins; D012333:RNA, Messenger; C087310:K cadherin