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.
CITATION STYLE
Loo, L. W. M., Gao, C., Shvetsov, Y. B., Okoro, D. R., Hernandez, B. Y., & Bargonetti, J. (2019). MDM2, MDM2-C, and mutant p53 expression influence breast cancer survival in a multiethnic population. Breast Cancer Research and Treatment, 174(1), 257–269. https://doi.org/10.1007/s10549-018-5065-7
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