The significance of sonic hedgehog immunohistochemical expression in colorectal carcinoma

Abstract

Colorectal carcinoma is a significant source of major morbidity and mortality. Sonic hedgehog (Shh) is expressed in normal gastrointestinal tract mucosa and in many malignancies. The purpose of the present study is to investigate the relationship between Shh immunoexpression in CRC and clinicopathological characteristics. Paraffin blocks of 155 primary CRCs and 37 nodal metastases were retrieved and tissue microarrays were constructed. Immunohistochemistry was performed using anti-Shh antibody. Immunostaining was scored and results were analysed in relation to the clinicopathological parameters. Shh was overexpressed in primary CRC (p=0.02) and in nodal metastasis (p=0.004). There was no difference between Shh immunoexpression in primary CRC and in nodal metastasis (p=0.941). High Shh immunoexpression was associated with well differentiated tumours (p=0.004). However, there was no association with other clinicopathological parameters. Shh overexpression was not associated disease free survival (log-rank=0.079, p=0.778). Shh is overexpressed in well differentiated CRC. However, Shh is not associated with other clinicopathological and prognostic factors. Loss of Shh may be associated with proliferation and loss of differentiation in CRC. Further molecular studies are required to address the potential importance of Shh signalling in CRC and to test Shh inhibitors and activators as potential therapeutic targets in CRC.