Reduced expression of Apaf-1 in colorectal adenocarcinoma correlates with tumor progression and aggressive phenotype
- Authors
- Paik, Seung Sam; Jang, Ki-Seok; Song, Young Soo; Jang, Si-Hyong; Min, Kyueng-Whan; Han, Hong Xiu; Na, Woong; Lee, Kang Hong; Choi, Dongho; Jang, Se Jin
- Issue Date
- Dec-2007
- Publisher
- SPRINGER
- Keywords
- colorectal cancer; apoptosis; apoptotic protease activating factor 1; tumor progression
- Citation
- ANNALS OF SURGICAL ONCOLOGY, v.14, no.12, pp.3453 - 3459
- Indexed
- SCIE
SCOPUS
- Journal Title
- ANNALS OF SURGICAL ONCOLOGY
- Volume
- 14
- Number
- 12
- Start Page
- 3453
- End Page
- 3459
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/172203
- DOI
- 10.1245/s10434-007-9541-2
- ISSN
- 1068-9265
- Abstract
- 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.
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