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Alpha tocopherol transfer protein (αTTP) is expressed in endometrial carcinoma and is correlated with FIGO stage and 5-year survival

  • Original Article – Cancer Research
  • Published:
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Abstract

Background

Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its transfer protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer.

Materials and methods

Ishikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. αTTP was detected by immunocytochemistry and western blot. αΤΤP expression was then assessed in 191 endometrioid endometrial carcinomas. Immunopositivity was correlated with grade, FIGO stage, and 5-year survival. Immuno-reactivity was assessed with a semi-quantitative score.

Results

AAPH- and BSO-induced αTTP expression in Ishikawa cells. Immunohistochemical assessment of the 191 endometrial cancer cases showed that αTTP expression correlated with FIGO stage (p = 0.014) but not with grade. Five-year survival was significantly better in cases of lower αTTP expression compared to cases with higher expression (p = 0.041).

Conclusions

The current results show that αTTP plays a role in endometrial carcinoma. Possibly endometrial cancer cells attempt to protect themselves from increasing oxidative stress by up-regulating αTTP. Selective molecular interventions targeting oxidative stress escape strategies, e.g., by overexpression of αTTP, could, therefore, allow oxidative stress to damage cancer cell membranes and thus restrict cancer progression.

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Acknowledgements

The authors thank Irmgard Wiest and Susanne Kunze for their excellent technical assistance. We would further like to acknowledge Jutta Engel and Max Wiedemann for their help with collecting follow-up data from the Munich Cancer Registry. SH received a Deutschlandstipendium scholarship from the Ludwigs-Maximilians-University of Munich. The funders had no role in study design, data collection and analysis, and decision to publish or preparation of the manuscript.

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    Authors and Affiliations

    1. Department of Obstetrics and Gynecology, Ludwig Maximilians University, Munich, Germany

      Sabine Heublein, Thomas Vrekoussis, Christina Kuhn & Udo Jeschke

    2. Department of Obstetrics and Gynecology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany

      Sabine Heublein & Gesine Faigle

    3. Division of Neonatology, Department of Pediatrics, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany

      Ronny Etzl

    4. Division of Gynecologic and Perinatal Pathology, Institute of Pathology, University of Leipzig, Leipzig, Germany

      Daisy Rotzoll

    5. LernKlinik Leipzig, University of Leipzig, Leipzig, Germany

      Daisy Rotzoll

    6. Department of Obstetrics and Gynecology, Medical School, University of Ioannina, Ioannina, Greece

      Iordanis Navrozoglou & Theodore Stefos

    7. Department of Obstetrics and Gynecology, Medical School, University of Crete, Heraklion, Greece

      Antonis Makrigiannakis

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    1. Sabine Heublein
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    Correspondence to Sabine Heublein.

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    S. Heublein and T. Vrekoussis contributed equally to this work.

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    Heublein, S., Vrekoussis, T., Etzl, R. et al. Alpha tocopherol transfer protein (αTTP) is expressed in endometrial carcinoma and is correlated with FIGO stage and 5-year survival. J Cancer Res Clin Oncol 143, 773–781 (2017). https://doi.org/10.1007/s00432-017-2340-7

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    • DOI: https://doi.org/10.1007/s00432-017-2340-7

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