A58

The Ovarian Cancer Tissue MicroArray Consortium

Susan Ramus¹, Martin Kbel², Dimitra Dafou¹, Elizabeth Benjamin³, Eva Wozniak¹, Estrid Hogdall⁴, Susanne Kruger Kjaer⁴, Lise Christensen⁵, Heidi Sowter⁶, Ahmad Al-Attar⁷, Richard Edmondson⁸, Steven Darby⁸, Mamatha Chivukula⁹, Kimberly Kalli¹⁰, Elaine Elliott¹⁰, Steve Kalloger², Kristy Driver¹¹, Martin Widschwendter¹, Aleksandra Gentry-Maharaj¹, Usha Menon¹

¹University College London, UK, ²BC Cancer Agency, Vancouver, Canada, ³Royal Free /UCL Medical School, London, UK, ⁴Danish Cancer Society, Copenhagen, Denmark, ⁵University of Copenhagen, Denmark, ⁶University of Derby, Derby, UK, ⁷University of Nottingham, UK, ⁸Northern Institute for Cancer Research, Newcastle, UK, ⁹Magee-Women's Hospital of UPMC, Pittsburgh, USA, ¹⁰Mayo Clinic, Rochester, USA, ¹¹University of Cambridge, UK

Background

Tissue microarrays (TMAs) can be used to rapidly analyse the expression status of candidate protein markers in large populations of tumours. We have established a consortium of studies with invasive epithelial ovarian cancer TMAs. Currently tumours from over 4,000 individuals are available and an additional 4,000 cases will be arrayed by mid 2010. Within this consortium are TMAs from cases from the Ovarian Cancer Association Consortium (OCAC) and from case only series, including clinical trials.

Method

A subset of these arrays, have been used to assess the role of a candidate tumour suppressor gene in ovarian cancer by immunohistochemistry (IHC). We are currently analysing a subset of the OCAC TMAs with a panel of 10 markers that can be used to classify the histopathological subtype. This will be used to determine the quality of the pathology data in the OCAC database to assess if centralised pathology review is required.

Results

For one candidate marker, EPB41L3, 66% of 794 invasive ovarian tumours showed no expression of the gene compared to only 24% of benign ovarian tumours and 0% of normal ovarian tissues. This result in combination with other functional assays shows this gene plays a role in ovarian cancer. Good concordance has been found between IHC profile and pathology report.

Discussion

These TMAs will be used in determining if candidate genes, identified by genome wide association studies (GWAS) and other studies, play a role in ovarian cancer and the large numbers should allow for stratification by histological subtype. The correct classification of histological subtype is of particular interest, as many of the genetic associations identified by OCAC appear to be specific to a particular subtype. Stage I and II GWAS data are available for 36% and 53% of the OCAC samples respectively and therefore the protein expression can be correlated with genotype.