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Nucleoside transporters are widely expressed in ovarian carcinoma effusions

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Abstract

Objective

Equilibrative and concentrative nucleoside transporters (ENTs and CNTs) mediate the cellular uptake of anticancer nucleosides and sensitivity to such compounds. We studied the expression of ENTs and CNTs in ovarian carcinoma effusions.

Methods

ENT1, ENT2, ENT4 and CNT3 expression was analyzed in 66 ovarian carcinoma effusions (61 peritoneal, 5 pleural) from 64 ovarian carcinoma patients by flow cytometry. The majority of patients received platinum-based chemotherapy. Results were analyzed for association with clinicopathologic parameters and survival.

Results

With the exception of one ENT2-negative effusion, ENT1, ENT2, ENT4 and CNT3 protein was detected on carcinoma cells in all effusions, with expression observed in 1–95% of tumor cells. Nucleoside transporter expression was comparable between peritoneal and pleural effusions and was unrelated to age, tumor grade, International Federation of Gynecology and Obstetrics (FIGO) stage, residual tumor volume after surgery, previous exposure to chemotherapy and response to chemotherapy at diagnosis (P > 0.05). No correlation was found between ENT or CNT expression and overall survival or progression-free survival, although higher ENT2 expression was associated with a trend for longer overall (45 vs. 23 months; P = 0.055) and progression-free (17 vs. 5 months; P = 0.087) survival.

Conclusion

Nucleoside transporters are frequently expressed in ovarian carcinoma effusions, but their expression generally appears to be unrelated to chemoresponse in this cancer in a cohort of patients treated by platinum-based chemotherapy. The role of ENT2 as a prognostic marker in this disease, as well as the role of these molecules in determining chemoresponse in patients treated by nucleoside analogs, merits further research.

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Acknowledgments

This study was supported by a grant from the Norwegian Cancer Society, by the Research Foundation of the Norwegian Radium Hospital and by the Inger and John Fredriksen Foundation for Ovarian Cancer Research. Annika J. Bock is the receiver of a MD/PhD student scholarship from the Faculty of Medicine, University of Oslo.

Conflict of interest

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Authors and Affiliations

  1. Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Montebello, 0424, Oslo, Norway

    Annika J. Bock, Hiep Phuc Dong, Björn Risberg & Ben Davidson

  2. Department of Gynecology, Oslo University Hospital, Ulleval, 0424, Oslo, Norway

    Annika J. Bock & Anne Cathrine Staff

  3. Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, 0424, Oslo, Norway

    Claes G. Tropé

  4. Faculty of Medicine, University of Oslo, 0316, Oslo, Norway

    Claes G. Tropé, Anne Cathrine Staff & Ben Davidson

  5. Institute for Medical Informatics, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

    Björn Risberg

Authors
  1. Annika J. Bock
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  2. Hiep Phuc Dong
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  3. Claes G. Tropé
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  4. Anne Cathrine Staff
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  5. Björn Risberg
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  6. Ben Davidson
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Correspondence to Ben Davidson.

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Bock, A.J., Dong, H.P., Tropé, C.G. et al. Nucleoside transporters are widely expressed in ovarian carcinoma effusions. Cancer Chemother Pharmacol 69, 467–475 (2012). https://doi.org/10.1007/s00280-011-1716-7

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  • DOI: https://doi.org/10.1007/s00280-011-1716-7

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