Examining the Relationship between Expression of Selected Tumour Associated Genes, Platelet Count and Survival in Ovarian Cancer
DJ Crowley, RJ Flavin, SA O'Toole, ST Aherne, PC Smyth, K Egan, E Dunne, D Kenny, JJ O'Leary, OM Sheils. Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland; Harvard Medical School, Boston, MA; Trinity Centre for Health Sciences, Trinity College Dublin, Dublin, Ireland; Royal College of Surgeons, Dublin, Ireland
Background: Ovarian cancer (OC) is the leading cause of death from gynaecological malignancy. It is a severe form of cancer with a mortality rate of ∼75% and a long term (5 year) survival rate of ∼20% associated with it. Up to half of patients diagnosed with ovarian cancer present with thrombocytosis – a blood platelet concentration of ≥ 450x109/L. This may be associated with Tumour Cell Induced Platelet Aggregation, observed to protect platelet 'cloaked' cancer cells from TNF-α and natural killer cell mediated destruction, chemotheraputic agents and enhancing their capability for metastasis.
Design: FFPE tissues corresponding to normal ovary (19), grade 2 (32), grade 2/3 (6) and grade 3 (43) ovarian cancer were sectioned. Total RNA was extracted with using Ambion RecoverAll Kits, before being reverse transcribed. cDNA samples were then PreAmplified for a panel of genes (PDGFα, PDGFRα, PDGFβ, PDGFRβ, VEGF, CA125, THPO and endogenous controls) before TaqMan RT-PCR was used to investigate the samples' gene expression. Relative Quantitation (RQ) was determined by 2-(ΔΔCt) method and significance by t-test using the Spotfire analysis suite and further analysis performed using SPSS.
Results: Significant (p<0.05) differences in expression of several target genes including CA125, VEGF, PDGFα+β, PDGFRα+β were observed. In cancer cases elevated PDGFβ expression was shown to correlate with preoperative thrombocytosis (p<0.05).
Conclusions: Variations in gene expression were observed with increasing tumour grades, with grades 2-3 displaying increased CA125 and VEGF expression (P<0.05) and a trend of reduced PDGFRα/β and increased PDGFβ expression (p<0.05) was observed. This supports previous histological observations in ovarian cancer. We propose that the ovarian tumour cells signal to encourage neovascularisation while remaining resistant to PDGF growth stimuli themselves, thus facilitating a microenvironment to sustain tumoural growth. In addition the correlation of elevated PDGFβ with elevated platelet levels suggests ovarian tumours may influence platelet production that may assist in their future metastasis.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 165, Wednesday Afternoon