Clusterin expression (CLU) as a prognostic marker in colorectal carcinoma (CCR).

Abstract

563 Background: Increased CLU is involved in malignant progression and anticlusterin treatment with antisense oligonucleotides enhances apoptosis induced by several citotoxics. However, clinical significance of CLU expression in human CRCs has been scarcely studied. We investigated whether changes in CLU could be related to carcinogenesis and survival (sv) of CRC patients (pts). Methods: Formalin-fixed and paraffin-embedded specimens were examined from 31 adenomas and 103 CRCs resected at Costa del Sol Hospital. The study was approved by Research Ethics Committee. Immunohistochemistry using monoclonal anti-α chain clusterin antibody (Upstate-Millipore, Watford, England) was performed, following standard staining procedure. CLU was scored as negative (CLU–) (no staining) or positive (CLU +) (>10% of tumor cells with strong staining). Cytoplasmic CLU in tumors was evaluated for cancer cells only, and in normal mucosa for epithelial cells only. Sv curves were calculated and plotted according to Kaplan-Meier method. Predictors that were significant at p<0.10 in univariate analysis, were entered into a Cox proportional hazards model for multivariate analysis, remaining significant at p<0.05. Results: Median follow-up was 54 months. Median age was 70 years (45-91). TNM stage distribution was: I (13%), II (48%), III (25%) and IV (14%). Epithelial normal cells were always CLU-, but 16% (5/31) of adenomas was CLU+ and this percentage increased in CRCs (30%, 31/103). Positive staining always presented an apical cytoplasmic pattern. Recurrence was more frequent in CLU+ (61%,19/ 31) than in CLU- tumors (37%, 27/72) and CLU was significantly associated with lower disease-free survival (DFS) (p<0.05). In multivariate analysis, CLU and stage remained significant independent prognostic factors for DFS (Table). Conclusions: CLU has a role in colon carcinogenesis and prognostic value. CLU is associated with decreased DFS among pts with CRCs. These findings have important implications for identifying CRC pts with more aggressive tumors who may benefit from targeted therapy against clusterin. [Table: see text]