title: Aurora B expression in metastatic effusions from advanced-stage ovarian serous carcinoma is predictive of intrinsic chemotherapy resistance.
abstract: The aim of the present study was to investigate the expression and clinical role of the aurora A and aurora B kinases in primary and metastatic serous ovarian carcinoma. AURKA and AURKB messenger RNA expression was investigated in 178 tumors (88 effusions, 38 primary carcinomas, and 52 solid metastases) from 144 patients with advanced-stage disease using quantitative real-time polymerase chain reaction. Aurora A and aurora B protein expression by immunohistochemistry was additionally analyzed in 147 tumors. Messenger RNA and protein expression at different anatomical sites were studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. AURKA and AURKB messenger RNA and their protein product were demonstrated in all primary carcinomas, solid metastases, and effusions. The expression of AURKA messenger RNA and aurora A protein was higher in effusions compared with solid specimens (P = .003 and P = .006, respectively). AURKB messenger RNA expression was higher in primary carcinomas, and solid metastases obtained prechemotherapy compared with postchemotherapy (P < .001 and P = .012, respectively), with no such difference in effusions (P > .05). Low aurora B protein expression was associated with primary chemotherapy resistance (P = .006) and poor treatment response (P = .013) in prechemotherapy effusions. No significant association was found between messenger RNA levels or protein expression and progression-free or overall survival. The present study documents for the first time frequent aurora A and aurora B expression in metastatic ovarian carcinoma, suggesting a role in cancer progression, with higher aurora A expression in effusions compared with primary carcinomas and solid metastases. Low AURKB messenger RNA expression in prechemotherapy effusions might be predictive of intrinsic chemotherapy resistance.
authors.affiliation: Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway.
authors.forename: Thea Eline
authors.initials: TE
authors.lastname: Hetland
authors.forename: Dag Andre
authors.initials: DA
authors.lastname: Nymoen
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.forename: Kjersti
authors.initials: K
authors.lastname: Brusegard
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
authors.forename: Janne
authors.initials: J
authors.lastname: Kærn
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D000077022:Survivin; D014404:Tubulin / Q000096:biosynthesis
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin; D014404:Tubulin; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt