Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Department of Biological Sciences Hunter College, The Graduate Center Departments of Biology and Biochemistry, City University of New York, New York, NY, 10016, USA.
Breast Cancer Res Treat. 2019 Feb;174(1):257-269. doi: 10.1007/s10549-018-5065-7. Epub 2018 Nov 23.
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.
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.
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.
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.
本研究旨在探讨突变型 p53（mtp53）、全长 MDM2（MDM2）和 MDM2 同种型 C（MDM2-C）的表达与多民族乳腺癌患者生存的关系。
使用商业上可用的针对 p53 和 MDM2 的抗体以及新开发的识别 MDM2-C 的单克隆抗体，对包含在一个临床注释的多民族人群基于组织微阵列（TMA）中的 787 例浸润性乳腺癌肿瘤进行了筛选。
mtp53 在较年轻（<50 岁）的乳腺癌患者中更为常见。在本研究中包含的 787 例病例中，mtp53、MDM2 和 MDM2-C 的表达与总生存率或乳腺癌特异性死亡率无显著相关性。然而，当在各个种族/民族群体（白种人、日本人、夏威夷原住民）内检查相关性时，仅发现 MDM2-C 的表达与白种人患者的乳腺癌特异性死亡率降低相关（HR 0.32，95%CI 0.15-0.69），mtp53 的表达与日本患者的总死亡率升高相关（HR 1.63，95%CI 1.02-2.59）。此外，MDM2-C 和 mtp53 联合表达阳性的日本患者的总死亡率风险增加两倍以上（HR 2.15，95%CI 1.04-4.48）；与各自种族/民族组中 MDM2-C 和野生型 p53 表达阴性的患者相比，MDM2-C 和野生型 p53 表达阳性的白种患者的死亡率风险降低（HR 0.28，95%CI 0.08-0.96）。
mtp53、MDM2 和 MDM2-C 的表达存在种族/民族差异，与乳腺癌特异性和总死亡率相关。MDM2-C 可能根据 mtp53 的表达而在乳腺癌发生中发挥积极或消极作用。
