title: Phospholipase D messenger RNA expression and clinical role in high-grade serous carcinoma.
abstract: The objective of this study was to analyze the expression and clinical role of phospholipase D (PLD) in high-grade serous carcinoma (HGSC). PLD1 and PLD2 isoform expression was studied in 125 HGSC specimens (73 effusions, 28 ovarian tumors, 24 solid metastases) using quantitative real-time reverse-transcription polymerase chain reaction. Expression levels were analyzed for association with clinicopathological parameters, including chemoresponse, and survival. PLD1 and PLD2 isoforms were found in most specimens at all anatomic sites, and their levels were strongly positively related (P<.001 for effusions and solid lesions). PLD2 messenger RNA (mRNA) expression was significantly higher in effusions compared with both carcinomas in the ovary and solid metastases (P<.001). Higher levels of both isoforms were associated with higher CA 125 levels at diagnosis (P<.001), and higher PLD2 mRNA levels in effusions were associated with unfavorable response to chemotherapy (P=.021). Expression levels of the studied isoforms were unrelated to the levels of previously studied mRNAs that form part of the phospholipase A2pathway or to survival. The present study provides the first evidence of PLD expression in HGSC and suggests a role in mediating progression to effusions and chemoresistance in this cancer.
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel; Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Harel-Dassa
authors.affiliation: Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Saul
authors.initials: S
authors.lastname: Yedgar
authors.affiliation: University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norway.
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
authors.affiliation: University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norway; Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway. Electronic address: bend@medisin.uio.no.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. Electronic address: reich@cc.huji.ac.il.
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000201:enzymology / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D010739:Phospholipase D / Q000235:genetics*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1
keywords: Chemotherapy; High-grade serous carcinoma; Phospholipase D; Survival; Tumor progression