Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer.
The clinical impact of circulating tumor cell (CTC) detection is controversial, mainly due to drawbacks of molecular approaches applied to this field. We sought to determine if the specific identification and counting of circulating tumor cells by cytomorphologic analysis has clinical usefulness. Peripheral blood (6 mL), treated using isolation by size of epithelial tumor cells, was obtained from 44 patients with primary liver cancer (PLC) and without metastases, 30 patients with chronic active hepatitis, 39 with liver cirrhosis, and 38 healthy individuals, and followed up for a mean period of 1 year. We searched for beta-catenin mutations in 60 single microdissected CTCs. One patient with liver cancer developed extrahepatic metastases during follow-up. CTCs and microemboli were found in 23 of the 44 patients with liver cancer and in none of the patients with chronic active hepatitis, patients with cirrhosis, or healthy subjects. Their presence was significantly associated with tumor diffusion (P =.0001) and portal tumor thrombosis (P =.006). Both the presence (P =.01) and number (P =.02) of CTCs and microemboli were significantly associated with a shorter survival. Beta-catenin mutations were found in 3 of 60 CTCs, arguing against their impact on the initial step of tumor cell invasion. In conclusion, the highly sensitive and specific detection of CTCs and microemboli may have clinical implications for cancer staging and outcome prediction. We also show the feasibility of molecular studies of individual circulating tumor cells, aimed at identifying gene mutations involved in tumor invasion.
Vona
Giovanna
G
Pasteur/INSERM Unit 370, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75739 Paris cedex 15, France.
Estepa
Laurence
L
Béroud
Christophe
C
Damotte
Diane
D
Capron
Frédérique
F
Nalpas
Bertrand
B
Mineur
Alexandra
A
Franco
Dominique
D
Lacour
Bernard
B
Pol
Stanislas
S
Bréchot
Christian
C
Paterlini-Bréchot
Patrizia
P
D000368:Aged; D002452:Cell Count; D003598:Cytoskeletal Proteins / Q000097:blood / Q000235:genetics; D004617:Embolism / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006521:Hepatitis, Chronic / Q000097:blood / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood* / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis; D013927:Thrombosis / Q000209:etiology; D015534:Trans-Activators / Q000097:blood / Q000235:genetics; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin