Circulating tumour cells detected by a novel adenovirus-mediated system may be a potent therapeutic marker in gynaecological cancers.
BACKGROUND
Recently developed detection system for circulating tumour cells (CTCs) using a telomerase-specific replicative adenovirus generated nonspecific green fluorescent protein (GFP) signals because of the co-presence of white blood cells (WBCs) nonspecifically infected by viruses. Here, we established a unique detection system for CTCs that completely excludes nonspecific signals.


METHODS
Blood obtained from the patients was subjected to haemolytic processes to eliminate red blood cells. The cell pellets were then infected with OBP-401, fixed, incubated with fluorescence-labelled anti-CD45 antibody to mark white blood WBCs, and examined on slides under a microscope.


RESULTS
Preparatory experiments with cancer cells artificially added to healthy donor samples confirmed that CD45 labelling could distinguish GFP-positive cancer cells from WBCs. In 53 patients with gynaecological cancers, CTCs were detected in 21 patients (39.6%) when CD45-positive cells were excluded as WBCs among GFP-positive cells. No CTCs were detected in samples from healthy volunteers. There was no significant correlation between CTC counts and known clinicopathological factors. The CTCs rapidly vanished after surgery or chemotherapy in most patients whose treatments were effective. In contrast, the persistence of CTCs even after treatments was tightly associated with poor response to the treatments (P<0.005).


CONCLUSIONS
The presence of CTCs in our system may potentially be a novel therapeutic marker in gynaecological cancers.
Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
M
M
Takakura
S
S
Kyo
M
M
Nakamura
Y
Y
Maida
Y
Y
Mizumoto
Y
Y
Bono
X
X
Zhang
Y
Y
Hashimoto
Y
Y
Urata
T
T
Fujiwara
M
M
Inoue
D000256:Adenoviridae / Q000737:chemistry*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D005833:Genital Neoplasms, Female / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000378:metabolism
D014408:Biomarkers, Tumor; D049452:Green Fluorescent Proteins; D019098:Telomerase; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human