Abstract 2492: Do disseminated tumor cells with stem cell character after therapy predict prognosis in primary ovarian cancer
Authors: Issam Chebouti, Christina Blassl, Pauline Wimberger, Hans Neubauer, Tanja Fehm, Rainer Kimmig, Sabine Kasimir-Bauer
Journal: Cancer Research (2016)

Abstract Background: We recently showed that the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of primary ovarian cancer patients (pts) significantly correlated with reduced progression free survival (PFS) and overall survival (OS). Here we analyzed whether the negative prognostic impact a) was related to the persistence of DTCs after platinum based chemotherapy and/or b) may arise from a cellular phenotype, being associated with stem cell character. Patients and Methods: 79 pts were studied for DTCs before (BT) and after therapy (AT) using immunocytochemistry applying the pan cytokeratin (CK) antibody A45-B/B3. Eight pts harboring at least five DTCs AT were analyzed on two additional cytospin slides by four immunofluorescence staining for DAPI, CK (FITC), SOX-2 or LIN-28 (TRITC), CD45 and CD43 (Cy5), respectively. A DTC was classified as a stem-like tumor cell in case of Dapipos, CD45neg, CD34neg, SOX-2pos/LIN-28pos and Ckpos or Ckneg as evaluated by microscopy. Results: DTCs were detected in 33/79 pts (42%) with a median number of four DTCs (range 1-37) BT and in 32/79 pts (41%) AT, median cell number eight DTCs (range 1-100), respectively. A persistence of DTCs was found in 13 pts, 20 pts were only positive before therapy, 19 pts after therapy and in 27 pts, no DTCs were detected at any time. Whereas the presence of DTCs BT significantly correlated with reduced OS (p = 0.024), pts initially DTCneg BT but DTCpos AT had a significant shorter PFS (p = 0.025). The persistence of DTCs resulted in a shorter PFS and OS reaching borderline significance (p = 0.06; p = 0.07). AT, Ckpos/LIN-28pos cells were detected in 9/10 patients [median two cells (range 1-5)] and Ckneg/LIN-28pos cells in 7/10 patients [median three cells (range 1-11)], respectively. For SOX-2, the results were 6/8 patients [median two cells (range-0-4)] and 7/8 patients [median four cells (range 1-11)], respectively. Interestingly, two further pts characterized as DTCneg AT but positive BT harbored 1-2 LIN-28pos and SOX-2pos cells in their BM AT. In cases vice versa, a few LIN-28 as well as SOX-2-positive cells were also present even BT. Conclusion: DTCs present AT express stem cell associated proteins and seem to be correlated with worse outcome. Furthermore, these cells were also detected in some cases BT which might explain worse outcome of pts who changed from DTCneg to DTCpos. Thus, additional therapeutic regimens may be necessary to eliminate these cells. Citation Format: Issam Chebouti, Christina Blassl, Pauline Wimberger, Hans Neubauer, Tanja Fehm, Rainer Kimmig, Sabine Kasimir-Bauer. Do disseminated tumor cells with stem cell character after therapy predict prognosis in primary ovarian cancer. [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 2492.