Poster Presentation 25th Lorne Cancer Conference 2013

High-grade mucinous ovarian cancer: from where does it originate and how should it be treated? (#393)

Matthew Wakefield 1 , Yoland Antill 2 , Kylie Gorringe 3 , Susie Bae 4 , Monique Topp 1 , Lara Lipton 5 , Winston Liauw 6 , Alex Boussioutas 3 , Michael Christie 5 , Michael Friedlander 7 , Stephen Fox 3 , Anna DeFazio 8 9 , David Bowtell 3 9 , Jan Pyman 10 , Ian Campbell 3 , Australian Ovarian Cancer Study (AOCS) 3 , Clare L Scott 1 10
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Monash University, Clayton, VIC, Australia
  3. Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia
  4. BioGrid Australia, Royal Melbourne Hospital, VIC, Australia
  5. Royal Melbourne Hospital, Parkville, VIC, Australia
  6. St George Hospital, Sydney, NSW, Australia
  7. Prince of Wales Hospital, Randwick, NSW, Australia
  8. Westmead Hospital, Sydney, NSW, Australia
  9. Australian Ovarian Cancer Study, Melbourne, Australia
  10. Royal Womens Hospital, Parkville, VIC, Australia

Background:  High-grade mucinous ovarian carcinoma (HG-MOC) is a rare sub-type of epithelial ovarian cancer that can occur in young women and is usually rapidly fatal. Resistance to the platinum-based regimens that are routinely used to treat ovarian cancer is common, and controversy exists over whether HG-MOC originate in the ovary or represent metastases from distant sites.

Hypothesis:  High-grade mucinous cancers found in the ovary share common genetic aberrations regardless of cell of origin and identifying the underlying aberrations may assist in the selection of optimal treatment for individual patients.

Methodology:  We will identify cases of rare HG-MOC via the rare tumour database, Cart-Wheel.org (BioGrid Australia) and via national and international tissue banks, including the Australian Ovarian Cancer Study. Cases with fresh frozen tissue available will be prioritized. FFPE blocks will be obtained for pathologic review and immunohistochemical analysis and HER2 in situ hybridization performed. Established guidelines will aid the diagnosis of primary versus secondary cancers found on the ovary. We will profile HG-MOC and metastases to the ovary using genome-wide technologies including targeted exon re-sequencing, RNA-seq and copy number analysis. We will compare HG-MOC with metastases from extra-ovarian sites eg colon/rectum, stomach and primary appendiceal pseudomyxoma peritoneii, as well as with borderline and low grade MOC (Gorringe, Campbell).

Results:  RNASeq data has been generated from one case each of primary HG-MOC, metastases from colon, gastric and appendix primary sites and one with neuroendocrine features. Relative molecular characteristics will be reported.

Conclusion:  If MOC and metastases are similar at the molecular level, this could change clinical trial design. Trials should then incorporate treatments, which better target regulatory pathways associated with this poor prognosis carcinoma, rather than approaches relevant for the organ from which the carcinoma was “thought” to be derived.