Circulating tumor cells: potential markers of minimal residual disease in ovarian cancer? a study of the OVCAD consortium - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Oncotarget Année : 2017

Circulating tumor cells: potential markers of minimal residual disease in ovarian cancer? a study of the OVCAD consortium

Résumé

Purpose: In 75% of ovarian cancer patients the tumor mass is completely eradicated by established surgical and cytotoxic treatment; however, the majority of the tumors recur within 24 months. Here we investigated the role of circulating tumor cells (CTCs) indicating occult tumor load, which remains inaccessible by established diagnostics. Experimental design: Blood was taken at diagnosis (baseline samples, n = 102) and six months after completion of adjuvant first-line chemotherapy (follow-up samples; n = 78). CTCs were enriched by density gradient centrifugation. A multi-marker immunostaining was established and further complemented by FISH on CTCs and tumor/metastasis tissues using probes for stem-cell like fusion genes MECOM and HHLA1. Results: CTCs were observed in 26.5% baseline and 7.7% follow-up blood samples at a mean number of 12.4 and 2.8 CTCs per ml blood, respectively. Baseline CTCs indicated a higher risk of death in R0 patients with complete gross resection (univariate: HR 2.158, 95% CI 1.111-4.191, p = 0.023; multivariate: HR 2.720, 95% CI 1.340-5.522, p = 0.006). At follow-up, the presence of CTCs was associated with response to primary treatment as assessed using RECIST criteria. Chromosomal gains at MECOM and HHLA1 loci suggest that the observed cells were cancer cells and reflect pathophysiological decisive chromosomal aberrations of the primary and metastatic tumors. Conclusions: Our data suggest that CTCs detected by the multi-marker protein panel and/or MECOM/HHLA1 FISH represent minimal residual disease in optimally debulked ovarian cancer patients. The role of CTCs cells especially for clinical therapy stratification of the patients has to be validated in consecutive larger studies applying standardized treatment schemes.
Fichier principal
Vignette du fichier
22468-317704-4-PB.pdf (1.9 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-02307472 , version 1 (08-06-2021)

Licence

Paternité

Identifiants

Citer

Eva Obermayr, Natalia Bednarz-Knoll, Béatrice Orsetti, Heinz-Ulrich Weier, Sandrina Lambrechts, et al.. Circulating tumor cells: potential markers of minimal residual disease in ovarian cancer? a study of the OVCAD consortium. Oncotarget, 2017, 8 (63), ⟨10.18632/oncotarget.22468⟩. ⟨hal-02307472⟩
87 Consultations
68 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More