title: Prognostic significance of cyclin D1, β-catenin, and MTA1 in patients with invasive ductal carcinoma of the breast.
abstract: BACKGROUND
  To investigate markers for predicting breast cancer progression, we performed a candidate gene-based study that assessed expression change of three genes, cyclin D1, β-catenin, and metastasis-associated protein-1 (MTA1), involving in aggressive phenotypes of cancerous cells, namely hyperproliferation, epithelial-mesenchymal transition, and global transcriptional regulation.
  
  
  METHODS
  Specimens were from 150 enrolled female patients, with invasive ductal carcinoma, followed up for more than 10 years. mRNA expression of cyclin D1, β-catenin, and MTA1 in cancerous and noncancerous cells microdissected from the primary tumor site was determined by quantitative real-time PCR. The relationship between mRNA expression levels of the genes and clinicopathologic features was assessed by statistical analysis. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan-Meier analysis with log-rank test and a multivariate Cox regression model.
  
  
  RESULTS
  Cyclin D1 was shown to be overexpressed in late-stage breast cancer (stage III/IV). Breast cancer with lymph node metastasis (LNM) showed significantly higher frequency of overexpressed cyclin D1, β-catenin, and MTA1 (P < 0.05). Patients carrying greater numbers of overexpressed genes had joint effects on increased risk in tumors of advanced stages (P ( trend ) = 0.03) and LNM (P ( trend ) < 0.01). In the LNM-negative group, patients whose tumors with greater number of cyclin D1, β-catenin, and MTA1 overexpressions were associated with poorer clinical outcomes, with hazard ratio of 14.79 for OS (P = 0.015) and 7.54 for DFS (P = 0.015) using multivariate Cox regression analysis during the 10-year follow-up.
  
  
  CONCLUSIONS
  Higher expression of cyclin D1, β-catenin, and MTA1 mRNAs in breast cancers may prove effective in predicting unfavorable outcomes of breast cancer.
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan. cwcheng@csmu.edu.tw
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Cheng
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.forename: Jyh-Cherng
authors.initials: JC
authors.lastname: Yu
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Shian-Ling
authors.initials: SL
authors.lastname: Ding
authors.forename: Chia-Ni
authors.initials: CN
authors.lastname: Hsiung
authors.forename: Huan-Ming
authors.initials: HM
authors.lastname: Hsu
authors.forename: Jia-Ching
authors.initials: JC
authors.lastname: Shieh
authors.forename: Pei-Ei
authors.initials: PE
authors.lastname: Wu
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D061346:Laser Capture Microdissection; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D015534:Trans-Activators; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; C089320:MTA1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; D006655:Histone Deacetylases