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Lung Resistance-Related Protein (LRP) Expression in Malignant Ascitic Cells as a Prognostic Marker for Advanced Ovarian Serous Carcinoma

  • Gynecologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Ovarian serous carcinoma is an aggressive cancer that often presents with metastatic disease. Although primary tumor and established metastatic foci in the omentum are generally compared to identify proteins involved in drug resistance, we investigated a potential bridge, the malignant cells from ascites, as facilitator of drug resistance and recurrence.

Methods

We evaluated the expression of drug resistance markers P-glycoprotein (P-gp), canalicular multispecific organic anion transporter (MRP2), and lung resistance-related protein (LRP) in malignant cells from ascites and matched omental metastasis from 25 patients with advanced-stage ovarian serous carcinoma who were chemotherapeutic naïve and undergoing initial cytoreductive surgery. Cell viability in vitro, patient response to chemotherapy, and patient survival were correlated with these biomarkers.

Results

Of the 25 patients evaluated for a correlation of LRP to 1-year recurrence, we correctly predicted the 1-year recurrence of 24 patients based solely on the presence of LRP in ascitic tumor cells (p = 0.01). P-gp and MRP2 were not expressed in malignant cells of ascites or omental metastases. Malignant cells from ascites had higher expression of LRP and were found to be more resistant to carboplatin treatment than cells from omental metastasis (p = 0.00375) by in vitro assay. LRP expression in the malignant cells of ascites correlated with carboplatin resistance (p = 0.001) by in vitro assay and recurrence at 1 year (p = 0.0125).

Conclusions

LRP expression in malignant cells of ascites is a promising marker to predict response to first-line chemotherapy in patients with advanced ovarian serous carcinoma.

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Acknowledgment

This project was supported by grants from the Kaleidoscope of Hope Ovarian Cancer Foundation to LRM and the Lupton Family Fellowship to EHK.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    Elizabeth H. Kerr MD, Cecil R. Stockard MS, Denise K. Oelschlager BS, Isam-Eldin Eltoum MD & William E. Grizzle MD, PhD

  2. Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA

    Peter J. Frederick MD

  3. Department of Surgery, University of Louisville, Louisville, KY, USA

    Michael E. Egger MD, Jeffery Sellers MS, Debbie DellaManna MS, Hope M. Amm PhD & Donald J. Buchsbaum PhD

  4. Department of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

    Peter J. Frederick MD & J. Michael Straughn MD

  5. Department of Medicine, University of Louisville James Brown Cancer Center, Louisville, KY, USA

    Lacey R. McNally PhD

Authors
  1. Elizabeth H. Kerr MD
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  2. Peter J. Frederick MD
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  3. Michael E. Egger MD
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  4. Cecil R. Stockard MS
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  6. Debbie DellaManna MS
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  7. Denise K. Oelschlager BS
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  8. Hope M. Amm PhD
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  9. Isam-Eldin Eltoum MD
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  10. J. Michael Straughn MD
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  11. Donald J. Buchsbaum PhD
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  12. William E. Grizzle MD, PhD
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  13. Lacey R. McNally PhD
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Corresponding author

Correspondence to Lacey R. McNally PhD.

Electronic supplementary material

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10434_2013_2878_MOESM1_ESM.pdf

Patients clinicopathological features Table 1 Legend: FIGO The International Federation of Gynecology and Obstetrics (PDF 12 kb)

10434_2013_2878_MOESM2_ESM.pdf

Patient’s malignant cells in ascites and omental metastasis were examined for LRP levels using Western blot. Patients 1 and 2 stained positive for LRP by IHC, whereas patient 3 stained negative for LRP by IHC (A = malignant cells in ascites; O = omental metastasis). Therefore, LRP expression by Western blot analysis correlated with LRP expression by IHC. Tumor cells from ascites fluid collected from patients with recurrent cancer also stained positive for LRP (patients A-F) (PDF 41 kb)

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Kerr, E.H., Frederick, P.J., Egger, M.E. et al. Lung Resistance-Related Protein (LRP) Expression in Malignant Ascitic Cells as a Prognostic Marker for Advanced Ovarian Serous Carcinoma. Ann Surg Oncol 20, 3059–3065 (2013). https://doi.org/10.1245/s10434-013-2878-9

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  • DOI: https://doi.org/10.1245/s10434-013-2878-9

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