Oral (16S134)

Altered expression of caspase-4 in colorectal polyps

Author(s)

D McSkeane1, B Flood2, J Fay3, J Manils2, F Alalawi4, M Tosetto4, H Mulcahy4, G Cullen4, K Sheahan4, EW Kay3, EJ Ryan4, GA Doherty4, EM Creagh2

Department(s)/Institutions

1Pathology Department, Bon Secours Hospital, Glasnevin, Dublin. 2School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland. 3RCSI and Beaumont Hospital, Dublin. 4Centre for Colorectal Disease, St. Vincent’s University Hospital and School of Medicine and Medical Sciences, University College Dublin, Ireland.

Introduction

Caspases are a family of cysteine proteases with established roles in cellular homeostasis, apoptosis and inflammation. Certain inflammatory caspases have been found to have altered activity in the development of intestinal diseases. Caspase-1 has been demonstrated to contribute to the intestinal inflammation observed during inflammatory bowel disease (IBD) and colorectal cancer (CRC). Two other related inflammatory caspases, caspase-4 and -5, are exclusively expressed in malignant intestinal epithelium cells of colorectal tumours, while their expression is absent from normal and inflamed epithelial tissue. Increased stromal expression of caspase-4 and -5 was also demonstrated in inflamed and dysplastic tissue. Polyps can be associated with inflammatory conditions such as IBD. These polyps may be either of a benign inflammatory nature or pre-cancerous adenomas which may progress to CRC.

Aims/Background

This study aimed to assess the involvement of inflammatory caspase-4 in four histological categories of colorectal polyp: hyperplastic (HPL), sessile serrated lesion (SSL), low grade dysplastic (LGD) and high grade dysplastic (HGD).

Method

IHC techniques were employed to examine the cellular expression profile of inflammatory caspase-4 in each category of colorectal polyp: HPL (n=18), SSL (n=10), LGD (n=19) and HGD (n=10).

Results

Caspase-4 is highly expressed in the epithelium of all four types of colorectal polyp, with a significant increase in the level of expression from LGD to HGD (p<0.01). Similarly, stromal expression also increased in relation to the degree of dysplasia with a significance between HGD and SSL (p<0.05) and HGD and HPL (p<0.05).

Conclusions

Caspase-4 expression profiles are increased in relation to the degree of dysplasia, thus identifying capsase-4 as a potential marker of dysplasia in colorectal polyps.