Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance -- a study of the OVCAD consortium
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Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance -- a study of the OVCAD consortium. / Obermayr, Eva; Castillo-Tong, Dan Cacsire; Pils, Dietmar; Speiser, Paul; Braicu, Ioana; Van Gorp, Toon; Mahner, Sven; Sehouli, Jalid; Vergote, Ignace; Zeillinger, Robert.
in: GYNECOL ONCOL, Jahrgang 128, Nr. 1, 01.01.2013, S. 15-21.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance -- a study of the OVCAD consortium
AU - Obermayr, Eva
AU - Castillo-Tong, Dan Cacsire
AU - Pils, Dietmar
AU - Speiser, Paul
AU - Braicu, Ioana
AU - Van Gorp, Toon
AU - Mahner, Sven
AU - Sehouli, Jalid
AU - Vergote, Ignace
AU - Zeillinger, Robert
N1 - Copyright © 2012. Published by Elsevier Inc.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - OBJECTIVE: The study aims at identifying novel markers for circulating tumor cells (CTCs) in patients with epithelial ovarian cancer (EOC), and at evaluating their impact on outcome.METHODS: Microarray analysis comparing matched EOC tissues and peripheral blood leucocytes (N=35) was performed to identify novel CTC markers. Gene expression of these novel markers and of EpCAM was analyzed using RT-qPCR in blood samples taken from healthy females (N=39) and from EOC patients (N=216) before primary treatment and six months after adjuvant chemotherapy. All samples were enriched by density gradient centrifugation. CTC positivity was defined by over-expression of at least one gene as compared to the healthy control group.RESULTS: CTC were detected in 24.5% of the baseline and 20.4% of the follow-up samples, of which two thirds were identified by overexpression of the cyclophilin C gene (PPIC), and just a few by EpCAM overexpression. The presence of CTCs at baseline correlated with the presence of ascites, sub-optimal debulking, and elevated CA-125 and HE-4 levels, whereas CTC during follow-up occurred more often in older and platinum resistant patients. PPIC positive CTCs during follow-up were significantly more often detected in the platinum resistant than in the platinum sensitive patient group, and indicated poor outcome independent from classical prognostic parameters.CONCLUSIONS: Molecular characterization of CTC is superior to a mere CTC enumeration or even be the rationale for CTC diagnostics at all. Ultimately CTC diagnostics may lead to more personalized treatment of EOC, especially in the recurrent situation.
AB - OBJECTIVE: The study aims at identifying novel markers for circulating tumor cells (CTCs) in patients with epithelial ovarian cancer (EOC), and at evaluating their impact on outcome.METHODS: Microarray analysis comparing matched EOC tissues and peripheral blood leucocytes (N=35) was performed to identify novel CTC markers. Gene expression of these novel markers and of EpCAM was analyzed using RT-qPCR in blood samples taken from healthy females (N=39) and from EOC patients (N=216) before primary treatment and six months after adjuvant chemotherapy. All samples were enriched by density gradient centrifugation. CTC positivity was defined by over-expression of at least one gene as compared to the healthy control group.RESULTS: CTC were detected in 24.5% of the baseline and 20.4% of the follow-up samples, of which two thirds were identified by overexpression of the cyclophilin C gene (PPIC), and just a few by EpCAM overexpression. The presence of CTCs at baseline correlated with the presence of ascites, sub-optimal debulking, and elevated CA-125 and HE-4 levels, whereas CTC during follow-up occurred more often in older and platinum resistant patients. PPIC positive CTCs during follow-up were significantly more often detected in the platinum resistant than in the platinum sensitive patient group, and indicated poor outcome independent from classical prognostic parameters.CONCLUSIONS: Molecular characterization of CTC is superior to a mere CTC enumeration or even be the rationale for CTC diagnostics at all. Ultimately CTC diagnostics may lead to more personalized treatment of EOC, especially in the recurrent situation.
KW - Adult
KW - Aged
KW - Antigens, Neoplasm
KW - CA-125 Antigen
KW - Cell Adhesion Molecules
KW - Cyclophilins
KW - Female
KW - Humans
KW - Middle Aged
KW - Neoplasms, Glandular and Epithelial
KW - Neoplastic Cells, Circulating
KW - Ovarian Neoplasms
KW - Prognosis
KW - Proteins
U2 - 10.1016/j.ygyno.2012.09.021
DO - 10.1016/j.ygyno.2012.09.021
M3 - SCORING: Journal article
C2 - 23017820
VL - 128
SP - 15
EP - 21
JO - GYNECOL ONCOL
JF - GYNECOL ONCOL
SN - 0090-8258
IS - 1
ER -