147P - Hox gene expression in ovarian cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Ovarian Cancer
Basic Science
Presenter Zoe Kelly
Authors Z. Kelly1, H. Pandha1, K. Madhuri2, R. Morgan1, A. Michael3
  • 1Department Of Microbial And Cellular Science, University of Surrey, GU27WG - Guildford/UK
  • 2Gynaecology And Surgery, Royal Surrey County Hospital, GU27XX - Guildford/UK
  • 3University of Surrey PGMS, Oncology, GU2 7WG - Guildford/UK

Abstract

Background

Ovarian cancer is the leading cause of cancer death among all gynaecological cancers. The aggressive nature of ovarian cancer is partly due to its heterogeneity and lack of effective treatment strategies other than surgery and standard chemotherapy. Further work to understand the molecular changes and design more effective drugs is essential. We have studied the expression of HOX genes-a family of homeodomain-containing transcription factors that determine cell and tissue identity in the early embryo and have been found to be dysregulated in cancer. We looked at the HOX gene expression profile of all 39 HOX genes in primary ovarian and peritoneal tumours of different histotypes.

Methods

HOX gene expression profiles were analysed in ovarian tumour samples and compared to normal ovarian tissue. RNA was isolated from tumour samples using the RNeasy® Plus Mini Kit (Qiagen Ltd) and the relative expression of all 39HOX genes were determined by quantitative real-time polymerase chain reaction. The 2-tailed student's t-test was applied to determine significant differences between tumours and normal ovary.

Results

We have analysed a cohort of 72 patients with epithelial ovarian cancer-59 serous, 5 endometrioid, 5 clear cell, 3 MMMT and one mucinous. Dysregulation of certain HOX genes expression was found in the majority of ovarian tumour samples with little to no expression in normal ovarian epithelium. By comparing HOX genes from all histotypes with normal ovarian tissue, 28 HOX genes were found to be upregulated in the tumours with P-values < 0.0001 for 20 genes. Expression of HOXB1, B2, B3, B7, B13, C11 and D12 were only seen in cancer tissue. HOXA9 and HOXB5 were found to be most highly expressed. The expression of HOXB5 was seen in 98% of the cancers analysed as compared with the normal ovarian tissue. The expression did not correlate with the clinical stage or CA-125 levels at presentation. The median follow up of the cohort was 26 months and median survival has not been reached.

Conclusion

HOX genes were shown to be dysregulated in ovarian tumours, with a number of genes showing significant upregulation compared to normal ovarian epithelium. HOXB5 and HOXA9 are the most highly up-regulated. This suggests that HOX genes may have a role in ovarian cancer oncogenesis.

Disclosure

All authors have declared no conflicts of interest.