A47: Characterisation of the oxysterol pathway in colorectal cancer

Rebecca Swan1,Abdo Alnabulsi1,Beatriz Cash2,Ayham Alnabulsi2,Graeme Murray1

1University of Aberdeen, Aberdeen, UK,2Vertebrate Antibodies, Aberdeen, UK

Presenting date: Monday 2 November
Presenting time: 12.20-13.10

Background

Colorectal cancer is one of the commonest types of cancer in the United Kingdom with many patients presenting at an advanced stage.  Despite the unequivocal value of current staging systems in colorectal cancer, there is a need to develop reliable prognostic biomarkers. Oxysterols are oxidised derivatives of cholesterol, formed by the enzymatic activity of several cytochrome P450 enzymes. Previous research has indicated that tumour-derived oxysterols are implicated in tumour growth and survival. The aim of this study was to profile the expression of 7 cholesterol-metabolising enzymes in primary colorectal cancer and assess the association between expression and prognosis.

Method

Immunohistochemistry was performed on a colorectal cancer tissue microarray containing 650 primary colorectal cancers using monoclonal antibodies to CYP2R1, CYP7B1, CYP8B1, CYP27A1, CYP39A1, CYP46A1 and CYP51A1, which we have developed.  The immunohistochemistry results were assessed by light microscopy using a semi-quantitative scoring system and correlated with clinico-pathological parameters including mismatch repair status and overall survival.

Results

All the antibodies were effective on formalin fixed wax embedded tissue. CYP2R1 (p<0.001), CYP7B1 (p<0.001), CYP8B1 (p<0.001), CYP46A1 (p<0.001) and CYP51A1 (p=0.001) were significantly overexpressed in primary colorectal cancer compared to normal colonic mucosa whereas CYP27A1 and CYP39A1 were not overexpressed in colorectal cancer. CYP7B1 (p=0.035), CYP39A1 (p=0.001), CYP46A1 (p<0.001) and CYP51A1 (p<0.001) showed reduced expression in lymph node metastasis compared with primary colorectal cancer. The presence of strong CYP8B1 immunoreactivity was associated with significantly reduced survival (?2=14.298, p<0.001). Immunoreactivity for CYP39A1 was associated with poorer survival compared to tumours with no CYP39A1 immunoreactivity (?2=10.21, p=0.001).

Conclusion

CYP2R1, CYP7B1, CYP8B1, CYP46A1 and CYP51A1 were significantly overexpressed in colorectal cancer.  Expression of CYP8B1 and CYP39A1 are strongly associated with poor survival.