Lenora W M Loo1, Chong Gao2, Yurii B Shvetsov3, Danielle R Okoro2, Brenda Y Hernandez3, Jill Bargonetti2. 1. Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA. lloo@cc.hawaii.edu. 2. Department of Biological Sciences Hunter College, The Graduate Center Departments of Biology and Biochemistry, City University of New York, New York, NY, 10016, USA. 3. Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Abstract
PURPOSE: The purpose of the study was to examine the association between expression of mutant p53 (mtp53), full-length MDM2 (MDM2), and MDM2 isoform C (MDM2-C) and survival in multiethnic breast cancer patients. METHODS: A total of 787 invasive breast tumors included in a clinically annotated multiethnic population-based tissue microarray (TMA) were screened utilizing commercially available antibodies to p53 and MDM2, and a newly developed monoclonal antibody recognizing MDM2-C. RESULTS: Mutant p53 (mtp53) was more common in younger (< 50 years) breast cancer patients. Among the 787 cases included in the study, mtp53, MDM2, and MDM2-C expression were not significantly associated with risk of overall or breast cancer-specific mortality. However when associations within individual racial/ethnic groups (White, Japanese, and Native Hawaiian) were examined, expression of MDM2-C was found to be associated with lower risk of breast cancer-specific mortality exclusively for White patients HR 0.32, 95% CI 0.15-0.69 and mtp53 expression was associated with higher overall mortality in Japanese patients (HR 1.63, 95% CI 1.02-2.59). Also, Japanese patients positive for the joint expression of MDM2-C and mtp53 had a greater than twofold risk of overall mortality (HR 2.15, 95% CI 1.04-4.48); and White patients with positive MDM2-C and wild-type p53 expression (HR 0.28, 95% CI 0.08-0.96) were at lower risk of mortality when compared to patients with negative MDM2-C and wild-type p53 expression in their respective racial/ethnic group. CONCLUSION: Racial/ethnic differences in expression profiles of mtp53, MDM2, and MDM2-C and associations with breast cancer-specific and overall mortality. MDM2-C may have a positive or negative role in breast tumorigenesis depending on mtp53 expression.
PURPOSE: The purpose of the study was to examine the association between expression of mutant p53 (mtp53), full-length MDM2 (MDM2), and MDM2 isoform C (MDM2-C) and survival in multiethnic breast cancerpatients. METHODS: A total of 787 invasive breast tumors included in a clinically annotated multiethnic population-based tissue microarray (TMA) were screened utilizing commercially available antibodies to p53 and MDM2, and a newly developed monoclonal antibody recognizing MDM2-C. RESULTS: Mutant p53 (mtp53) was more common in younger (< 50 years) breast cancerpatients. Among the 787 cases included in the study, mtp53, MDM2, and MDM2-C expression were not significantly associated with risk of overall or breast cancer-specific mortality. However when associations within individual racial/ethnic groups (White, Japanese, and Native Hawaiian) were examined, expression of MDM2-C was found to be associated with lower risk of breast cancer-specific mortality exclusively for White patients HR 0.32, 95% CI 0.15-0.69 and mtp53 expression was associated with higher overall mortality in Japanese patients (HR 1.63, 95% CI 1.02-2.59). Also, Japanese patients positive for the joint expression of MDM2-C and mtp53 had a greater than twofold risk of overall mortality (HR 2.15, 95% CI 1.04-4.48); and White patients with positive MDM2-C and wild-type p53 expression (HR 0.28, 95% CI 0.08-0.96) were at lower risk of mortality when compared to patients with negative MDM2-C and wild-type p53 expression in their respective racial/ethnic group. CONCLUSION: Racial/ethnic differences in expression profiles of mtp53, MDM2, and MDM2-C and associations with breast cancer-specific and overall mortality. MDM2-C may have a positive or negative role in breast tumorigenesis depending on mtp53 expression.
Entities:
Keywords:
Breast cancer; MDM2; MDM2-C; Multiethnic; P53; Survival
Authors: Jinjun Dang; Mei-Ling Kuo; Christine M Eischen; Lilia Stepanova; Charles J Sherr; Martine F Roussel Journal: Cancer Res Date: 2002-02-15 Impact factor: 12.701
Authors: E Tamborini; G Della Torre; C Lavarino; A Azzarelli; P Carpinelli; M A Pierotti; S Pilotti Journal: Int J Cancer Date: 2001-06-15 Impact factor: 7.396
Authors: A D Thor; I I Moore DH; S M Edgerton; E S Kawasaki; E Reihsaus; H T Lynch; J N Marcus; L Schwartz; L C Chen; B H Mayall Journal: J Natl Cancer Inst Date: 1992-06-03 Impact factor: 13.506
Authors: Jordan S Fridman; Eva Hernando; Michael T Hemann; Elisa de Stanchina; Carlos Cordon-Cardo; Scott W Lowe Journal: Cancer Res Date: 2003-09-15 Impact factor: 12.701