Loss of APAF-1 expression is associated with early recurrence in stage I, II, and III colorectal cancer.

Abstract

Apoptotic protease activating factor-1 (APAF-1) is a key regulator in the mitochondrial apoptotic pathway and an important diagnostic and therapeutic biomarker. Loss of APAF-1 expression has been observed in various tumors including colorectal cancer. The aim of our study was to evaluate the relationship between loss of APAF-1 expression and early recurrence of stage I-III colorectal cancer. We investigated 165 out of 492 patients who had undergone curative resection for colorectal cancer between 1991 and 2001. Sixty-one patients (37.0%) had early recurrence within 1year after surgery. Tissue microarrays were used for immunohistochemical detection of APAF-1. The mean age of patients with recurrence was 58years (range, 24-85); 88 (53.3%, 88/165) were male. APAF-1 was expressed in 32 (19.4%, 32/165) cases and was not expressed in 133 (80.6%, 133/165). In univariate analysis, early recurrence significantly correlated with loss of APAF-1 expression (p = 0.017), tumor stage (p = 0.005), N category (p = 0.001), and lymphatic invasion (p = 0.008). In a logistic regression model, loss of APAF-1 expression (p = 0.015, 95% CI = 1.280-10.063) and N category (p = 0.001, 95% CI = 0.004-0.739) proved to be independent risk factors associated with early recurrence. In patients with lymph node metastasis, early recurrence was more frequent in the APAF-1-negative group than in the APAF-1-positive group (46.2% (54/117) vs. 22.2% (6/27), p = 0.023). Loss of APAF-1 expression is associated with early recurrence in stage I-III colorectal cancer, suggesting that APAF-1 may have clinical value as a predictive marker of early recurrence.