Detection of occult cancer cells in peripheral blood and bone marrow by quantitative RT-PCR assay for cytokeratin-7 in breast cancer patients.
The clinical significance of occult micrometastasis (O.M) remains unknown. We investigated it in peripheral blood (P.B.) and bone marrow (B.M.) in breast cancer patients with surgery. First, we investigated the expression levels of 7 representative molecular markers for detecting O.M (CEA, CK-7, CK-18, CK-19, CK-20, MAM and MUC-1) in 27 cancer and 8 non-epithelial cell lines using quantitative RT-PCR (QRT-PCR), and showed that the expression level of CK-7 was higher in every cancer cell line than in the non-epithelial cell lines. Next, we studied the clinical significance of O.M in P.B. and B.M. by QRT-PCR for CK-7 in breast cancer patients with surgery. Based on comparison with 17 non-cancer controls, 37 (18.0%) and 100 (48.5%) of the 206 patients were positive for CK-7 in P.B. and B.M., respectively. In 98 cases observed over 24 months after surgery, the CK-7-positive group in P.B. had poorer disease-free survival (DFS) than the negative group (p<0.01). The CK-7-positive group in P.B. showed poorer DFS than the negative group in 132 lymph node-negative cases (p=0.01), and moreover, in 61 lymph node-negative cases observed over 24 months after surgery, the CK-7-positive group in P.B. showed poorer DFS than the negative group (p<0.0001). In B.M., no significant difference in DFS was found between the CK-7-positive and CK-7-negative groups. QRT-PCR for CK-7 could be a useful and universal method for detecting O.M, and the quantitative detection of CK-7 in P.B. would have a prognostic value as a marker of early recurrence in breast cancer patients with surgery.
Masuda
Taka-Aki
TA
Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Kataoka
Akemi
A
Ohno
Shinji
S
Murakami
Shigeru
S
Mimori
Koshi
K
Utsunomiya
Tohru
T
Inoue
Hiroshi
H
Tsutsui
Shinichi
S
Kinoshita
Junko
J
Masuda
Norikazu
N
Moriyama
Noriyuki
N
Mori
Masaki
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001853:Bone Marrow / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053552:Keratin-7; D007633:Keratins / Q000032:analysis* / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C507497:KRT7 protein, human; D053552:Keratin-7; D007633:Keratins