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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2013

01-09-2013 | Gynecologic Oncology

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

Authors: Elizabeth H. Kerr, MD, Peter J. Frederick, MD, Michael E. Egger, MD, Cecil R. Stockard, MS, Jeffery Sellers, MS, Debbie DellaManna, MS, Denise K. Oelschlager, BS, Hope M. Amm, PhD, Isam-Eldin Eltoum, MD, J. Michael Straughn, MD, Donald J. Buchsbaum, PhD, William E. Grizzle, MD, PhD, Lacey R. McNally, PhD

Published in: Annals of Surgical Oncology | Issue 9/2013

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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.
Appendix
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Literature
1.
2.
3.
4.
Goldstein LJ, Pastan I, Gottesman MM. Multidrug resistance in human cancer. Crit Rev Oncol Hematol. 1992;12:243–53.PubMedCrossRef
5.
Bradley G, Ling V. P-glycoprotein, multidrug resistance and tumor progression. Cancer Metastasis Rev. 1994;13:223–33.PubMedCrossRef
6.
Taniguchi K, Wada M, Kohno K, et al. A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res. 1996;56:4124–9.PubMed
7.
Kool M, de Hass M, Scheffer GL, et al. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res. 1997;57:3537–47.PubMed
8.
Arts HJ, Katsaros D, de Vries EG, et al. Drug resistance-associated markers P-glycoprotein, multidrug resistance-associated protein 1, multidrug resistance-associated protein 2, and lung resistance protein as prognostic factors in ovarian carcinoma. Clin Cancer Res. 1999;5:2798–805.PubMed
9.
Izquierdo MA, Scheffer GL, Schroeijers AB, et al. Vault-related resistance to anticancer drugs determined by the expression of the major vault protein LRP. Cytotechnology. 1998;27:137–48.PubMedCrossRef
10.
Kedersha NL, Rome LH, Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA. J Cell Biol. 1986;103:699–709.PubMedCrossRef
11.
Rome L, Kedersha N, Chugani D, Unlocking vaults: organelles in search of a function. Trends Cell Biol. 1991;1:47–50.PubMedCrossRef
12.
Oda Y, Ohishi Y, Basaki Y, et al. Prognostic implications of the nuclear localization of Y-box-binding protein-1 and CXCR4 expression in ovarian cancer: their correlation with activated Akt, LRP/MVP and P-glycoprotein expression. Cancer Sci. 2007;98:1020–6.PubMedCrossRef
13.
Yakirevich, E, Sabo E, Naroditsky I, et al. Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas. Gynecol Oncol. 2006;100:152–9.PubMedCrossRef
14.
Goff BA, Paley PJ, Greer BE, et al. Evaluation of chemoresistance markers in women with epithelial ovarian carcinoma. Gynecol Oncol. 2001;81:18–24.PubMedCrossRef
15.
Goff BA, Ries JA, Els LP, et al. Immunophenotype of ovarian cancer as predictor of clinical outcome: evaluation at primary surgery and second-look procedure. Gynecol Oncol. 1998;70:378–85.PubMedCrossRef
16.
Shield K, Ackland ML, Ahmed N, et al. Multicellular spheroids in ovarian cancer metastases: biology and pathology. Gynecol Oncol. 2009;113:143–8.PubMedCrossRef
17.
Comin CE, Saieva C, Messerini L. h-Caldesmon, calretinin, estrogen receptor, and Ber-EP4: a useful combination of immunohistochemical markers for differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary. Am J Surg Pathol. 2007;31:1139–48.PubMedCrossRef
18.
Ordonez NG. The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study. Mod Pathol. 2006;19:34–48.PubMedCrossRef
19.
Estes JM, Oliver PG, Straughn JM Jr, et al. Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human ovarian carcinoma using a novel ex vivo tissue slice model. Gynecol Oncol. 2007;105:291–8.PubMedCrossRef
20.
Frederick PJ, Kendrick JE, Straughn JM Jr, et al. Effect of TRA-8 anti-death receptor 5 antibody in combination with chemotherapy in an ex vivo human ovarian cancer model. Int J Gynecol Cancer. 2009;19:814–9.PubMedCrossRef
21.
Grizzle WE. Tissue resources in the detection and evaluation of markers. In: Srivastava S, editor. Early detection of cancer: molecular markers. Armonk: Futura Publishing Co., 1997:69–76.
22.
Casey RC, Burleson KM, Skubitz KM, et al. Beta 1-integrins regulate the formation and adhesion of ovarian carcinoma multicellular spheroids. Am J Pathol. 2001;159:2071–80.PubMedCrossRef
23.
Burleson KM, Casey RC, Skubitz KM, et al. Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol. 2004;93:170–81.PubMedCrossRef
24.
Burleson KM, Boente MP, Pambuccian SE, et al. Disaggregation and invasion of ovarian carcinoma ascites spheroids. J Transl Med. 2006;4:6.PubMedCrossRef
25.
Inch WR, McCredie JA, Sutherland RM. Growth of nodular carcinomas in rodents compared with multi-cell spheroids in tissue culture. Growth. 1970;34:271–82.PubMed
26.
Rustin GJS, Timmers P, Nelstrop A, et al. Comparison of CA-125 and standard definitions of progression of ovarian cancer in the Intergroup trial of cisplatin and paclitaxel versus cisplatin and cyclophosphamide. J Clin Oncol. 2006;24:45–51.PubMedCrossRef
27.
Lee CK, Friedlander M, Brown C, et al. Absence of early decline in CA125 is a poor surrogate for benefit of liposomal doxorubicin and carboplatin treatment in the CALYPSO study. J Natl Cancer Inst. 2011;103:1338–42.PubMedCrossRef
Metadata
Title
Lung Resistance-Related Protein (LRP) Expression in Malignant Ascitic Cells as a Prognostic Marker for Advanced Ovarian Serous Carcinoma
Authors
Elizabeth H. Kerr, MD
Peter J. Frederick, MD
Michael E. Egger, MD
Cecil R. Stockard, MS
Jeffery Sellers, MS
Debbie DellaManna, MS
Denise K. Oelschlager, BS
Hope M. Amm, PhD
Isam-Eldin Eltoum, MD
J. Michael Straughn, MD
Donald J. Buchsbaum, PhD
William E. Grizzle, MD, PhD
Lacey R. McNally, PhD
Publication date
01-09-2013
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 9/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-2878-9

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