Aurora B expression in metastatic effusions from advanced-stage ovarian serous carcinoma is predictive of intrinsic chemotherapy resistance

• Published in: Human pathology 2013-05, Vol.44 (5), p.777-785
• Main Authors: Hetland, Thea Eline, MD, Nymoen, Dag Andre, MSc, Holth, Arild, BSc, Brusegard, Kjersti, MSc, Flørenes, Vivi Ann, PhD, Kærn, Janne, MD, PhD, Tropé, Claes G., MD, PhD, Davidson, Ben, MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aurora Kinase A; Aurora Kinase B; Aurora Kinases; Carcinoma, Ovarian Epithelial; Chemotherapy; Chemotherapy response; Cystadenocarcinoma, Serous - metabolism; Cystadenocarcinoma, Serous - pathology; Drug Resistance, Neoplasm - genetics; Effusions; Female; Humans; Inhibitor of Apoptosis Proteins - biosynthesis; Kinases; Middle Aged; Neoplasm Metastasis - pathology; Neoplasm Metastasis - physiopathology; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - pathology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Pathology; Patients; Pleural Effusion, Malignant - metabolism; Pleural Effusion, Malignant - pathology; Protein-Serine-Threonine Kinases - biosynthesis; Proteins; Proto-Oncogene Proteins c-akt - biosynthesis; RNA, Messenger - metabolism; Surgery; Survival; Survivin; Tubulin - biosynthesis; Tumor progression
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2012.08.002

Summary 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.