Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance -- a study of the OVCAD consortium

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 -