The role of apoptosis in colorectal carcinogenesis and its prognostic value.

Abstract

e22131 Background: Most colorectal cancers (CRCs) progress through a multistep process from normal tissue to adenoma to carcinoma. The role of apoptosis during this tumourigenesis sequence has not yet been completely clarified. The aim of our study was to determine the influence of apoptotic variations on the carcinogenesis and prognosis of CRC. Methods: A TUNEL assay was performed on the formalin-fixed, paraffin-embedded tissues from 103 CRCs resected at the Costa del Sol Hospital (after excluding patients previously treated with chemotherapy or radiation therapy), 26 adenomas and 20 samples of normal epithelia. Clinical data were obtained from the tumour registry and hospital charts. The study was approved by Research Ethics Committee. We used the median (m) of apoptotic percentage (1%, range: 0-6%) as a threshold value for survival (sv) studies. Analysis of association between apoptosis and prognostic factors used the X2test for categorical variables and the analysis of variance test for continuous variables (natural log transformed if necessary). We estimated sv using the Kaplan-Meier method, and sv curves were compared with the log rank test. Cox’s proportional hazards sv analysis was used to determine the relative risk (RR) through multivariate analyses. Results: Median follow-up was 50 months (mo). Apoptotic index (AI) was higher in CRCs (1.09 ± 0.13) than in adenomas (0.38 ± 0.23, p=0.059) and significantly greater than in normal epithelium (0.06 ± 0.04, p=0.001). AI was greater in stage IV than in other stages (p=0.017). Higher AI was associated with lower disease-free survival (DFS) and overall survival (OS) than lower AI (Table). In multivariate analysis, AI (RR=2.18, 95% CI 1.08-4.37) and TNM stage (RR=2.41, 95% CI 1.20-4.85) were independent prognostic factors for OS. Conclusions: Our study demonstrates an increase in apoptosis during colorectal carcinogenesis and a correlation between apoptotic rates and survival. Higher AIs are associated with more aggressive tumours and a poorer prognosis in CRC. [Table: see text]