title: Lung resistance-related protein (LRP) expression in malignant ascitic cells as a prognostic marker for advanced ovarian serous carcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Kerr
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Frederick
authors.forename: Michael E
authors.initials: ME
authors.lastname: Egger
authors.forename: Cecil R
authors.initials: CR
authors.lastname: Stockard
authors.forename: Jeffery
authors.initials: J
authors.lastname: Sellers
authors.forename: Debbie
authors.initials: D
authors.lastname: DellaManna
authors.forename: Denise K
authors.initials: DK
authors.lastname: Oelschlager
authors.forename: Hope M
authors.initials: HM
authors.lastname: Amm
authors.forename: Isam-Eldin
authors.initials: IE
authors.lastname: Eltoum
authors.forename: J Michael
authors.initials: JM
authors.lastname: Straughn
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Buchsbaum
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: Lacey R
authors.initials: LR
authors.lastname: McNally
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001201:Ascites / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D016190:Carboplatin / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D016190:Carboplatin; D008840:Microfilament Proteins; D017239:Paclitaxel; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C412617:KLHL1 protein, human