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p85 Protein Expression is Associated with Poor Survival in HER2-Positive Patients with Advanced Breast Cancer Treated with Trastuzumab

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Pathology & Oncology Research

Abstract

To investigate the immunohistochemical expression of p85 in a cohort of trastuzumab-treated HER2-positive and HER2-negative metastatic breast cancer patients. The medical records of all patients with metastatic breast cancer treated with trastuzumab-based regimens between 1998 and 2010 were reviewed and clinical information was obtained. Formalin-fixed paraffin-embedded tumor tissue samples with adequate material were retrospectively collected from 183 patients. Samples were evaluated by immunohistochemistry for p85, estrogen receptors (ER), progesterone receptors (PgR), HER2, Ki67, PTEN and phosphorylated Akt (S473 and T308). HER2 status was studied by fluorescence in situ hybridization, as well. PIK3CA mutational status was also evaluated. Median follow-up for all patients was 72 months. Central re-evaluation for HER2 revealed only 111 HER2-positive cases, with the remaining 72 patients being HER2-negative. Median survival was longer in HER2-positive patients (50.7 months) compared to HER2-negative patients (36.6 months) both treated with trastuzumab, but this difference has not reached significance (p = 0.068). In total, 62 % of the patients were found positive for p85, however the p85 protein was not found to be differentially expressed in HER2-positive versus HER2-negative cases. There were no significant associations between protein expression of p85 and any of the markers under study, or with time to progression. Positive p85 protein expression was however associated with poor survival in trastuzumab-treated HER2-positive patients. In our cohort of trastuzumab-treated HER2-positive breast cancer patients, positive p85 protein expression appears to be a prognostic factor of poor survival and, if validated, might have important implications in the treatment of such patients.

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Acknowledgments

We would like to thank Thalia Spinari for tissue collection, Dimitra Katsala for monitoring the study and Maria Moschoni for coordinating the data management.

The study was supported by a Hellenic Cooperative Oncology Group grant HER_11P/05 and a research grant from Roche Hellas SA.

Competing Interests

The authors declare that they have no competing interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethical Approval

The translational research protocol has been approved by the Bioethics Committee of the Aristotle University of Thessaloniki School of Medicine (Protocol # 4283; January 14, 2008) under the general title “Investigation of major mechanisms of resistance to treatment with trastuzumab in patients with metastatic breast cancer”. All patients included in the study after 2005 provided written informed consent for the provision of biological material for future research studies, before receiving any treatment. Waiver of consent was obtained from the Bioethics Committee for patients included in the study before 2005.

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Authors and Affiliations

  1. Pathology Department, Athens University Medical School, Athens, Greece

    Kitty Pavlakis & Anastasios Stofas

  2. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

    Mattheos Bobos & George Fountzilas

  3. Department of Pathology, Ioannina University Hospital, Ioannina, Greece

    Anna Batistatou

  4. Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

    Vassiliki Kotoula

  5. Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece

    Anastasia G. Eleftheraki

  6. Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

    Eleni Timotheadou, Konstantine T. Kalogeras & George Fountzilas

  7. Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

    George Pentheroudakis

  8. Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece

    Amanda Psyrri

  9. Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece

    Angelos Koutras

  10. Oncology Section, Second Department of Internal Medicine, “Hippokration” Hospital, Athens, Greece

    Dimitrios Pectasides

  11. Department of Medical Oncology, “Hippokration” Hospital, Athens, Greece

    Pavlos Papakostas

  12. Third Department of Medical Oncology, “Hygeia” Hospital, Athens, Greece

    Evangelia Razis

  13. Second Department of Medical Oncology, “Metropolitan” Hospital, Piraeus, Greece

    Christos Christodoulou

  14. Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece

    Konstantine T. Kalogeras

Authors
  1. Kitty Pavlakis
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  2. Mattheos Bobos
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  3. Anna Batistatou
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  4. Vassiliki Kotoula
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  5. Anastasia G. Eleftheraki
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  6. Anastasios Stofas
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  7. Eleni Timotheadou
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  8. George Pentheroudakis
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  9. Amanda Psyrri
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  10. Angelos Koutras
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  11. Dimitrios Pectasides
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  12. Pavlos Papakostas
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  13. Evangelia Razis
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  14. Christos Christodoulou
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  15. Konstantine T. Kalogeras
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  16. George Fountzilas
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Corresponding author

Correspondence to Kitty Pavlakis.

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Pavlakis, K., Bobos, M., Batistatou, A. et al. p85 Protein Expression is Associated with Poor Survival in HER2-Positive Patients with Advanced Breast Cancer Treated with Trastuzumab. Pathol. Oncol. Res. 21, 273–282 (2015). https://doi.org/10.1007/s12253-014-9818-2

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  • DOI: https://doi.org/10.1007/s12253-014-9818-2

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