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Virchows Archiv

, Volume 464, Issue 6, pp 701–707 | Cite as

BUB1 mRNA is significantly co-expressed with AURKA and AURKB mRNA in advanced-stage ovarian serous carcinoma

  • Ben DavidsonEmail author
  • Dag Andre Nymoen
  • Bente Vilming Elgaaen
  • Anne Cathrine Staff
  • Claes G. Tropé
  • Janne Kærn
  • Reuven Reich
  • Thea E. Hetland Falkenthal
Original Article

Abstract

The objective of this study was to investigate the expression and clinical role of the spindle checkpoint kinase budding uninhibited by benzimidazole 1 (Bub1) in primary and metastatic advanced-stage ovarian serous carcinoma. BUB1 mRNA expression was analyzed 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 (PCR). Bub1 protein expression by Western blotting was studied in 63 carcinomas (30 effusions and 33 solid lesions). BUB1 mRNA expression at different anatomic sites was studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. BUB1 mRNA was universally expressed in serous carcinomas, irrespective of anatomic site. BUB1 mRNA levels were uniformly low in six ovarian surface epithelium specimens analyzed for comparative purposes. Bub1 protein was expressed in 22/30 effusions and 28/33 solid lesions. BUB1 mRNA expression was significantly higher in chemo-naïve primary carcinomas and solid metastases compared to specimens obtained following neoadjuvant chemotherapy (p < 0.001) and was unrelated to chemotherapy exposure in effusions nor to chemoresponse or survival at any anatomic site. BUB1 mRNA levels in both effusions and solid lesions were strongly related to the mRNA levels of AURKA and AURKB previously studied in this cohort (p < 0.001 for both). Bub1 is widely expressed in primary and metastatic OC, suggesting a biological role in this cancer. BUB1 mRNA levels are lower following chemotherapy exposure in solid lesions, though its presence is unrelated to clinical behavior including response to chemotherapy and survival. BUB1 is co-expressed with AURKA and AURKB suggesting biological relationship between these spindle cell components.

Keywords

Bub1 Ovarian carcinoma Tumor progression Effusions Chemotherapy response Survival 

Notes

Acknowledgment

This work was supported by the Inger and John Fredriksen Foundation for Ovarian Cancer Research.

Conflict of interest statement

We declare that we have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ben Davidson
    • 1
    • 2
    Email author
  • Dag Andre Nymoen
    • 1
  • Bente Vilming Elgaaen
    • 3
  • Anne Cathrine Staff
    • 2
    • 4
  • Claes G. Tropé
    • 2
    • 5
  • Janne Kærn
    • 5
  • Reuven Reich
    • 6
  • Thea E. Hetland Falkenthal
    • 3
  1. 1.Department of Pathology, Oslo University HospitalNorwegian Radium HospitalOsloNorway
  2. 2.University of Oslo, Faculty of MedicineInstitute of Clinical MedicineOsloNorway
  3. 3.Department of Oncology, Oslo University HospitalOsloNorway
  4. 4.Department of Obstetrics and GynaecologyOslo University HospitalOsloNorway
  5. 5.Department of Gynecologic Oncology, Oslo University HospitalNorwegian Radium HospitalOsloNorway
  6. 6.Institute of Drug Research, School of Pharmacy, Faculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael

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