Background: Resistance to platinum based chemotherapy in ovarian cancer can only be assessed retrospectively during post-chemotherapy follow-up. We recently showed that excision-repair cross-complementing rodent repair deficiency complementation group 1 nuclease (ERCC1)-positive (+) circulating tumor cells (CTCs) were an independent predictor for progression free survival (PFS), overall survival (OS) and for platinum-resistance in our ovarian cancer patients (pts). We now analyzed whether the negative prognostic impact of CTCs was related to the presence and persistence of ERCC1+ CTCs after platinum based chemotherapy.
Methods: 10 ml blood of 65 primary ovarian cancer pts before and after chemotherapy were studied for CTCs by immunomagnetic enrichment followed by multiplex RT-PCR to detect the transcripts EpCAM, MUC-1 and Ca 125 (AdnaTest OvarianCancer; QIAGEN Hannover GmbH, Germany). A patient was considered CTC+, if at least one of the three markers was detectable. ERCC1 was analyzed in a separate approach by single plex PCR, ß-actin served as an internal control and PCR-products were quantified on the Agilent Bioanalyzer 2100.
Results: CTCs were detected in 18/65 pts (28%) before and in 13/65 pts (20%) after chemotherapy. A persistence of CTCs was found in four pts, 14 pts were only positive before and nine pts only after therapy whereas in 38 pts, no CTCs were detected at any time. Pts with persisting CTCs had a significantly shorter PFS (p = 3.32E-05) and OS (0.00018) while pts initially CTC-negative before but CTC+ after therapy showed a reduced OS (p = 0.0039). ERCC1+CTCs were observed in 12/65 (18%) pts before and in 8/65 pts (12%) after therapy. A persistence of ERCC1+CTCs was found in three pts, nine pts were only positive before, five pts only after therapy whereas in 48 pts, no ERCC1+CTCs were detected at any time. Pts with persisting ERCC1+CTCs had a significantly shorter PFS (p = 0.032) and OS (0.0058) while pts initially ERCC1-negative before but ERCC1+ after therapy showed a reduced OS (p = 0.039). Up to now, no association between clinically defined platinum resistance and ERCC1-positivity was observed.
Conclusion: The negative prognostic impact of CTCs was related to the presence and persistence of ERCC1+CTCs after therapy supporting the idea to implement ERCC1 expression in CTC analysis of ovarian cancer pts as a biomarker for monitoring the disease to possibly change treatment in case of ERCC1 persistent CTCs.
Citation Format: Issam Chebouti, Paul Buderath, Jan Dominik Kuhlmann, Yvonne Bokeloh, Siggi Hauch, Rainer Kimmig, Sabine Kasimir-Bauer. The presence and persistence of ERCC1 positive circulating tumor cells predicts worse prognosis in primary ovarian cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 447.