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10.1245/s10434-007-9541-2
Annals of Surgical Oncology 14:3453-3459 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Reduced Expression of Apaf-1 in Colorectal Adenocarcinoma Correlates with Tumor Progression and Aggressive Phenotype

Seung Sam Paik, MD1, Ki-Seok Jang, MD1, Young Soo Song, MD1, Si-Hyong Jang, MD1, Kyueng-Whan Min, MD1, Hong Xiu Han, MD1, Woong Na, MD1, Kang Hong Lee, MD2, Dongho Choi, MD3 and Se Jin Jang, MD4

1 Departments of Pathology, College of Medicine, Hanyang University, Seoul, Korea
2 Departments of Surgery, College of Medicine, Hanyang University, Seoul, Korea
3 Department of Surgery, College of Medicine, Soon Chun Hyang University, Seoul, Korea
4 Department of Pathology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea

Correspondence: Address correspondence and reprint requests to: Se Jin Jang, MD; E-mail: jangsejin{at}amc.seoul.kr

Background: Apoptotic protease activating factor-1 (Apaf-1) is one of the key regulators in the mitochondrial apoptotic pathway, and the loss of Apaf-1 leads to cellular resistance against the apoptotic signals. We investigated the expression of Apaf-1 in colorectal tissues corresponding to the multistep carcinogenesis model to determine correlations between the clinicopathologic characteristics and the expression of this molecule and to evaluate the role of Apaf-1 in the development and progression of colorectal adenocarcinoma.

Methods: Immunohistochemistry for Apaf-1 was performed on the tissue microarray of 38 normal mucosal tissues, 46 adenomatous polyps, 529 colorectal adenocarcinomas, and 76 metastatic tumors.

Results: Normal colonic mucosa tissues and adenomas were positive for Apaf-1 with no exceptions (100%). However, in colorectal adenocarcinomas, 119 of 529 cases (22.5%) were positive and 410 cases (77.5%) were negative. Moreover, 67 of 76 metastatic cases (88.2 %) were negative and only nine cases (11.8%) were positive for Apaf-1 expression. In the analyses between Apaf-1 expression and clinicopathologic parameters, reduced expression of Apaf-1 correlated with left colon location (p < 0.001), deeper tumor invasion (p < 0.001), frequent lymph node metastasis ( p= 0.021), higher American Joint Committee on Cancer (AJCC) and Dukes’ stage (p = 0.02 and p = 0.001, respectively) and poorer differentiation (p < 0.001). The patient survival was significantly associated with age, histological grade, AJCC stage, and lymphovascular invasion, but not Apaf-1 expression (p = 0.478).

Conclusions: The results suggest that the loss of Apaf-1 expression is a relatively frequent late event and the loss of Apaf-1 expression may play an important role in tumorigenesis and tumor progression in colorectal adenocarcinoma.

Key Words: Colorectal cancer • Apoptosis • Apoptotic protease activating factor 1 • Tumor progression






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