Clusterin expression in gastrointestinal neuroendocrine tumours is highly correlated with location and is helpful in determining the origin of liver metastases

Aims Clusterin ( CLU ) is a sulphated glycoprotein implicated in many physiological and pathological processes, including tumorigenesis. We have previously demonstrated that CLU is highly expressed in pancreatic neuroendocrine tumours ( NET s). The aims of this study were: to investigate CLU expression in gastrointestinal NET s; the potential correlation between this expression and different clinicopathological parameters; and its usefulness in the differential diagnosis of liver metastases. Methods and results Immunohistochemistry using an anti‐ CLU antibody was performed on paraffin sections from 108 primary NET s [ G 3 (13 cases), G 2 (18 cases), and G 1 (77 cases), according to the 2010 WHO classification] and 60 metastases. Cytoplasmic positivity was scored qualitatively and quantitatively. The pattern of staining was also assessed. Two‐step statistical analyses (univariate and multivariate logistic regression) were performed. More than 90% of small‐intestine NET s were completely negative. The probability of obtaining a positive CLU score was higher for the appendix, the stomach, the duodenum and the rectum than for the small intestine and colon. All G 3 NET s and most G 2 NET s were negative as compared with G 1. CLU expression in the metastatic foci was identical to that of the primary tumour. Conclusions Clusterin expression in gastrointestinal NET s is highly correlated with location and probably also with grading, in both the primary tumour and metastases. Underexpression of CLU in small‐intestine NET s is helpful for identifying the origin of liver metastases: a strong CLU score in a liver biopsy makes the small intestine highly unlikely as a primary site.