Bo Wook Kim1,2, Hanbyoul Cho3, Kris Ylaya1, Haruhisa Kitano1,4, Joon-Yong Chung1, Stephen M Hewitt5, Jae-Hoon Kim6. 1. Experimental Pathology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, U.S.A. 2. Department of Obstetrics and Gynecology, International St. Mary's Hospital, Catholic Kwandong University, Incheon, Republic of Korea. 3. Department of Obstetrics and Gynecology, Gangnam Severance Hospital, College of Medicine, Yonsei University, Seoul, Republic of Korea. 4. Department of Thoracic Surgery, Shiga University of Medical Science, Otsu, Japan. 5. Experimental Pathology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, U.S.A. genejock@helix.nih.gov jaehoonkim@yuhs.ac. 6. Department of Obstetrics and Gynecology, Gangnam Severance Hospital, College of Medicine, Yonsei University, Seoul, Republic of Korea genejock@helix.nih.gov jaehoonkim@yuhs.ac.
Abstract
BACKGROUND/AIM: Bcl-2-like protein 11 (BIM) is a pro-apoptotic member of the Bcl-2 protein family. BIM elicits cell death by binding to pro-survival Bcl-2 proteins. Even though the association of BIM expression with cell death has been investigated, its clinical survival significance in cervical cancer has not. In the current study, the prognostic significance of BIM in cervical cancer was investigated. PATIENTS AND METHODS: The study included normal cervical tissues (n=254), cervical intraepithelial neoplasia (CIN) tissues (n=275), and invasive cervical cancer (n=164). In order to identify BIM expression, immunohistochemistry (IHC) was performed, and IHC scoring by quantitative digital image analysis was determined. Then, the association of BIM with prognostic factors was investigated. RESULTS: BIM expression was higher in cervical cancer than normal cervical tissues (p<0.001). Well and moderate differentiation indicated higher BIM expression than did poor differentiation (p=0.001). Also, BIM expression was high in radiation-sensitive cervical cancer relative to radiation-resistant cancer (p=0.049). High BIM expression showed better 5-year disease-free survival (DFS) and overall survival (OS) rates (p=0.049 and π=0.030, respectively) than did low expression. In a multivariate analysis, BIM was shown to be an independent risk factor for DFS and OS in cervical cancer, with hazard ratios of 0.22 (p=0.006) and 0.46 (p=0.046), respectively. CONCLUSION: BIM is associated with favorable prognostic markers for prediction of DFS and OS in cervical cancer. High BIM expression is a potential prognostic marker as well as a chemotherapeutic target for cervical cancer. Copyright
BACKGROUND/AIM: Bcl-2-like protein 11 (BIM) is a pro-apoptotic member of the Bcl-2 protein family. BIM elicits cell death by binding to pro-survival Bcl-2 proteins. Even though the association of BIM expression with cell death has been investigated, its clinical survival significance in cervical cancer has not. In the current study, the prognostic significance of BIM in cervical cancer was investigated. PATIENTS AND METHODS: The study included normal cervical tissues (n=254), cervical intraepithelial neoplasia (CIN) tissues (n=275), and invasive cervical cancer (n=164). In order to identify BIM expression, immunohistochemistry (IHC) was performed, and IHC scoring by quantitative digital image analysis was determined. Then, the association of BIM with prognostic factors was investigated. RESULTS:BIM expression was higher in cervical cancer than normal cervical tissues (p<0.001). Well and moderate differentiation indicated higher BIM expression than did poor differentiation (p=0.001). Also, BIM expression was high in radiation-sensitive cervical cancer relative to radiation-resistant cancer (p=0.049). High BIM expression showed better 5-year disease-free survival (DFS) and overall survival (OS) rates (p=0.049 and π=0.030, respectively) than did low expression. In a multivariate analysis, BIM was shown to be an independent risk factor for DFS and OS in cervical cancer, with hazard ratios of 0.22 (p=0.006) and 0.46 (p=0.046), respectively. CONCLUSION:BIM is associated with favorable prognostic markers for prediction of DFS and OS in cervical cancer. High BIM expression is a potential prognostic marker as well as a chemotherapeutic target for cervical cancer. Copyright
Authors: Mauricio J Reginato; Kenna R Mills; Jessica K Paulus; Danielle K Lynch; Dennis C Sgroi; Jayanta Debnath; Senthil K Muthuswamy; Joan S Brugge Journal: Nat Cell Biol Date: 2003-08 Impact factor: 28.824