Preoperative u-PAR gene expression in bone marrow indicates the potential power of recurrence in breast cancer cases.
BACKGROUND
The clinical significance of isolated tumor cells (ITC) in peripheral blood (PB) and bone marrow (BM) as predictive markers in the recurrence or metastasis of breast cancer has not yet been determined. In the current study, we focused on the urokinase plasminogen activator receptor (u-PAR) gene as a powerful indicator of the potential to relapse after surgery.


METHODS
We examined CK-7 and CK19 as an ITC marker and u-PAR as a candidate indicator for metastasis in PB and BM from 800 cases of breast cancer by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). Serum tumor markers, carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3), were compared with u-PAR or CK status.


RESULTS
CK7 in PB was positive in 262 cases that showed a poorer disease-free survival (DFS) than 478 CK7(-) cases (P < 0.05). The 153 cases of u-PAR(+) in BM showed significantly poorer DFS and overall survival (OS) than did the 579 cases of u-PAR(-) in BM (P < 0001 and P < 0.0001, respectively). In PB, a significant difference was also observed between 330 cases of u-PAR(+) and 437 cases of u-PAR(-) (P < 0.0001). The hazard ratio (HR) for prediction of recurrence was significantly higher in u-PAR (P < 0.0001; HR 0.0519) than the level of three serum tumor markers.


CONCLUSIONS
u-PAR expresses in cancer cells during the dormant phase. The current findings revealed that the expression levels of u-PAR in PB and BM evaluated preoperatively indicate the potential to relapse or metastasize after surgery.
Mimori
Koshi
K
Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Kataoka
Akemi
A
Yamaguchi
Hiroshi
H
Masuda
Norikazu
N
Kosaka
Yoshimasa
Y
Ishii
Hideshi
H
Ohno
Shinji
S
Mori
Masaki
M
D001853:Bone Marrow; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D015870:Gene Expression; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D011237:Predictive Value of Tests; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics*; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator