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Serum Midkine Correlates with Tumor Progression and Imatinib Response in Gastrointestinal Stromal Tumors

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

A previous study identified midkine (MK) expression in primary gastrointestinal stromal tumor (GIST) as a prognostic marker. The aim of the current study was to compare serum midkine (S-MK) concentrations of GIST patients with those of healthy controls and to determine if MK can serve as a prognostic serum marker for these patients.

Materials and Methods

S-MK concentrations were measured by enzyme-linked immunosorbent assay in GIST patients (n = 96) and healthy controls (n = 148). S-MK levels were then correlated with clinicopathological data and the administration of imatinib therapy. In addition, MK expression was evaluated in 39 surgically resected GIST and in 17 leiomyoma specimens on a tissue microarray.

Results

S-MK concentrations in GIST patients were significantly higher than in healthy controls: median (25th and 75th percentiles) S-MK concentration was 235 (139 and 376) pg/ml in the GIST patients and 99 (33 and 198) pg/ml in the controls (P < 0.001; Mann–Whitney U test). Significantly higher median S-MK concentrations were found in GIST with recurrence compared with those without (295 vs 230; P = 0.009). GIST patients with S-MK levels higher than 400 pg/ml showed a significantly worse recurrence-free survival (P = 0.026; log-rank test). Patients receiving imatinib therapy had decreased median S-MK concentrations compared with those who were not treated with imatinib (331 vs 201; P < 0.001).

Conclusions

S-MK concentration is a potential marker for evaluating the progression and prognosis of GIST, especially during imatinib therapy. Further studies could focus on the role of midkine in the tumorigenesis of GIST and responsiveness toward imatinib therapy.

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Acknowledgment

We thank Sabine Schmidt for her excellent technical assistance. We thank the patients who willingly and generously provided data and samples for research purposes.

Financial Support

This study was funded by research grants from the Dr. Mildred Scheel Stiftung (German Cancer Aid) and supported by a Research Grant from Novartis Oncology, Switzerland.

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Authors and Affiliations

  1. Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Tamina Rawnaq MD, Miriam Kunkel MS, Kai Bachmann MD, Hilke Zander PhD, Jakob R. Izbicki MD & Jussuf T. Kaifi MD

  2. Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Ronald Simon PhD & Guido Sauter MD

  3. Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Stephan Brandl MD

Authors
  1. Tamina Rawnaq MD
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  2. Miriam Kunkel MS
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  3. Kai Bachmann MD
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  4. Ronald Simon PhD
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  5. Hilke Zander PhD
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  6. Stephan Brandl MD
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  8. Jakob R. Izbicki MD
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  9. Jussuf T. Kaifi MD
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Corresponding author

Correspondence to Tamina Rawnaq MD.

Additional information

This study was funded by research grants from the Dr. Mildred Scheel Stiftung (German Cancer Aid) and supported by a Research Grant from Novartis Oncology, Switzerland.

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Rawnaq, T., Kunkel, M., Bachmann, K. et al. Serum Midkine Correlates with Tumor Progression and Imatinib Response in Gastrointestinal Stromal Tumors. Ann Surg Oncol 18, 559–565 (2011). https://doi.org/10.1245/s10434-010-1191-0

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  • DOI: https://doi.org/10.1245/s10434-010-1191-0

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