Oncotarget

Research Papers:

Analysis of disseminated tumor cells before and after platinum based chemotherapy in primary ovarian cancer. Do stem cell like cells predict prognosis?

Issam Chebouti _, Christina Blassl, Pauline Wimberger, Hans Neubauer, Tanja Fehm, Rainer Kimmig and Sabine Kasimir‑Bauer

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Oncotarget. 2016; 7:26454-26464. https://doi.org/10.18632/oncotarget.8524

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Abstract

Issam Chebouti1,*, Christina Blassl2,*, Pauline Wimberger3, Hans Neubauer2, Tanja Fehm2, Rainer Kimmig1, Sabine Kasimir-Bauer1

1Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany

2Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany

3Department of Gynecology and Obstetrics, Carl-Gustav-Carus University, TU Dresden, Dresden, Germany

*These authors have contributed equally to this work

Correspondence to:

Issam Chebouti, e-mail: [email protected]

Keywords: disseminated tumor cells, bone marrow, stem cells, primary ovarian cancer

Received: December 02, 2015     Accepted: February 21, 2016     Published: April 01, 2016

ABSTRACT

Background: We recently reported that the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of primary ovarian cancer patients (POC pts) correlated with reduced progression free survival (PFS) and overall survival (OS). Here we analyzed whether the negative prognostic influence was related to DTC persistence after platinum based chemotherapy and/or due to DTCs associated with stem cell character.

Results: DTCs were detected in 33/79 pts (42%) before and in 32/79 pts (41%) AT. Persistent DTCs were found in 13 pts, 20 pts were only positive BT, 19 pts AT and 27 pts had no DTCs. Whereas the presence of DTCs BT significantly correlated with reduced OS (p = 0.02), pts initially DTCneg BT but DTCpos AT had a significantly shorter PFS (p = 0.03). DTC persistence resulted in a shorter PFS and OS reaching borderline significance (p = 0.06; p = 0.07). LIN-28-and SOX-2 positive cells were detected in all eight pts AT.

Patients and Methods: 79 POC pts were studied for DTCs before therapy (BT) and after therapy (AT) using immunocytochemistry. Eight pts harboring at least five DTCs AT were further analyzed on two additional slides by four-fold immunofluorescence staining for DAPI, Cytokeratin (CK), SOX-2 or LIN-28, CD45 and CD34 (Cy5). A stem-like tumor cell was classified as Dapipos, CD45neg, CD34neg, SOX-2pos/LIN-28pos and CKpos or CKneg.

Conclusions: Stem cell associated proteins are expressed in DTCs that are present AT and their presence seem to be correlated with a worse outcome. Additional therapeutic regimens may be necessary to eliminate these cells.


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