title: Amplification of Mdmx and overexpression of MDM2 contribute to mammary carcinogenesis by substituting for p53 mutations.
abstract: BACKGROUND
  The p53 tumor suppressor gene is mutated or deleted in nearly half of human cancers. The murine double minute 2 (Mdm2) and Mdmx represent two important cellular regulators of p53. The aim of this study was to evaluate the abnormalities of p53, Mdmx and Mdm2 genes in archived breast cancers.
  
  
  METHODS
  We assessed the genetic instability at p53, Mdmx and Mdm2 using high resolution multi-color fluorescent in situ hybridization (FISH) protocol and detected the expression status of the tumor protein p53 (TP53), MDMx and MDM2 by immunohistochemistry in 115 archived samples of infiltrating ductal breast carcinomas with foci of ductal carcinoma in situ (DCIS) components.
  
  
  RESULTS
  The presence of p53 allelic loss and/or TP53 overexpression was observed in 38% out of all patients, and was significantly more often in larger, high grade, ER negative and high ki67 tumors. Mdmx amplification with low-level increase of gene copy number is at high frequency while Mdm2 amplification is rare in primary breast cancer. Mdmx amplification was seen in more invasive carcinomas than preinvasive lesions. MDMx and MDM2 overexpression were detected in 65% and 38% of all cases respectively. Moreover it was showed that most tumors contained either p53 dysfunction or Mdm2 alteration, but not both. This distribution was significant (P < 0.05). Inverse correlation between Mdmx amplification/overexpression and p53 disfunction was also observed (P < 0.05).
  
  
  CONCLUSIONS
  Our results suggest the involvement of Mdm2 and Mdmx in p53-independent breast carcinogenesis and Mdmx may contribute to the regulation of p53 independently of Mdm2.
  The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1450529994118798.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Mu
authors.forename: Zhishuang
authors.initials: Z
authors.lastname: Li
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Meng
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shandong University School of Medicine, 44#,Wenhua Xi Road, 250012 Jinan, Shandong, PR, China. lillie6636@sdu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics; D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2