Levels of Lipid Peroxidation Are an Important Stimulus in Driving the Adenoma-Carcinoma Sequence in Colorectal Cancer
A Maguire, M Biniecka, R Geraghty, J Hyland, D O'Donoghue, H Mulcahy, J O'Sullivan, K Sheahan. St. Vincent's University Hospital, Dublin, Ireland; University College Dublin, Dublin, Ireland
Background: Oxidative stress can result in lipid peroxidation. 4-Hydroxy-2-nonenal (4-HNE) is the main aldehyde formed during lipid peroxidation of 6-polyunsaturated fatty acids by superoxide and is a crucial mediator of oxidative stress. 4-HNE is known to be mutagenic in mammalian cells. Mitochondria are also targets of 4-HNE where 4-HNE adduct formation can alter many mitochondrial functions. The role of lipid peroxidation in driving the adenoma-carcinoma sequence in colorectal cancer (CRC) is unknown.
Design: Tissue microarrays were constructed for 39 contiguous adenomas, 51 synchronous adenomas and their matched colorectal cancer and non-neoplastic tissue. 41 adenomas from patients with no history of colorectal carcinoma were also examined. Immunohistochemistry for 4-HNE was performed and semi-quantitatively scored for both epithelial and stromal cell staining. Percentage positivity and intensity of nuclear and cytoplasmic staining 4HNE was scored for both cell types in all tissues. Data was statistically analysed using the Wilcoxon signed rank test.
Results: Epithelial nuclear expression of 4-HNE is higher in non-neoplastic tissue and synchronous adenomas compared to matched carcinomas (p values all <0.02). Epithelial nuclear intensity of 4-HNE is significantly higher in synchronous adenomas and non-neoplastic tissue compared to carcinomas (p values all <0.002). Expression of cytoplasmic (but not nuclear) 4-HNE is lowest in epithelium of non-neoplastic tissue (10%), increased in synchronous adenomas (56%) and contiguous adenomas (62%) and highest in carcinomas (75%) (p values all <0.05).
Conclusions: Levels of nuclear 4-HNE are higher in non-neoplastic tissue and adenomas compared to matched carcinomas. This may point to a role for nuclear 4-HNE in the initiation of the adenoma-carcinoma sequence. Levels of cytoplasmic 4-HNE which is mitochondrial in nature, increase during the adenoma-carcinoma sequence suggesting a potential role for lipid peroxidation and it's effect on mitochondria in neoplastic progression.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 98, Monday Morning