Elevated Lipid Peroxidation and Cyclin D1 Levels Correlate with Poor Survival and Disease Recurrence in Stage II Tumours.
Cara Dunne, Aoife Maguire, Monika Biniecka, Miriam Tosetto, John Hyland, Kieran Sheahan, Diarmuid O'Donoghue, Hugh Mulcahy, Jacintha O'Sullivan. St Vincent's University Hospital, Dublin, Ireland; St James' Hopsital and Trinity College, Dublin, Ireland
Background: 30% of stage II patients relapse within 5 years with survival similar to Stage III disease. Studies investigating what molecular markers segregate Stage II patients likely to relapse and benefit from treatment are warranted. Using disease specific colorectal arrays, we identified significant alterations in cyclin D1 gene levels and DNA damage markers in this cohort. We hypothesise that expression of Cyclin D1 at the protein level will segregate good and poor Stage II tumours.
Design: We assessed Cyclin D and a lipid peroxidation marker, 4HNE in 260 Stage II cases. Tissue microarrays were constructed using four 0.6mm cores from each tumour and matched normal tissue. The percentage positive staining and intensity of both markers were assessed for epithelial and stroma cells. Results were correlated with patient outcome data.
Results: High levels of nuclear 4HNE expression in epithelium cells of stage II tumours correlated with poor patient survival (p=0.003). In contrast to tumour tissue, high 4HNE cytoplasmic expression in epithelium and stroma cells of normal adjacent tissue correlated with good survival (p=0.000 and p=0.010 respectively). High levels of nuclear Cyclin D1 expression in the stroma in stage II tumours correlated with poor patient survival (p=0.001). In addition high levels of Cyclin D1 cytoplasmic and nuclear expression in the epithelium of normal adjacent tissue correlated with poor survival (p=0.008, p=0.038). A strong association was detected between cyclin D1 and expression of a glycoprotein, Clusterin (p<0.001).
Conclusions: High cyclin D1 and lipid peroxidation levels segregates good and poor stage II tumours.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 45, Wednesday Morning