Byung Kyu Ahn1, Sung Hoo Kim1, Seung Sam Paik2, Kang Hong Lee3. 1. Department of Surgery, College of Medicine, Hanyang University, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 133-792, Korea. 2. Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea. 3. Department of Surgery, College of Medicine, Hanyang University, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 133-792, Korea. leekh@hanyang.ac.kr.
Abstract
PURPOSE: 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. METHODS: 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 1 year after surgery. Tissue microarrays were used for immunohistochemical detection of APAF-1. RESULTS: The mean age of patients with recurrence was 58 years (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). CONCLUSIONS: 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.
PURPOSE: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. METHODS: 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 1 year after surgery. Tissue microarrays were used for immunohistochemical detection of APAF-1. RESULTS: The mean age of patients with recurrence was 58 years (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). CONCLUSIONS: 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.
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