title: Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study.
abstract: BACKGROUND
  The ubiquitin-proteasome system (UPS) plays a pivotal role in tumorigenesis. Components of the UPS have recently been implicated in breast cancer progression. In the present study, we sought to explore the prognostic and/or predictive significance of UBE2C messenger RNA (mRNA) expression on disease-free survival (DFS) and overall survival (OS) in high-risk operable breast cancer patients.
  
  
  METHODS
  Five hundred and ninety-five high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative, dose-dense sequential chemotherapy with epirubicin followed by CMF (cyclophosphamide, methotrexate and 5-fluorouracil) with or without paclitaxel (Taxol). RNA was extracted from 313 formalin-fixed primary tumor tissue samples followed by one-step quantitative RT-PCR for assessment of mRNA expression of UBE2C.
  
  
  RESULTS
  High UBE2C mRNA expression was associated with poor DFS (Wald's P = 0.003) and OS (Wald's P = 0.005). High tumor grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of UBE2C. Results of the Cox multivariate regression analysis revealed that high UBE2C mRNA expression remained an independent adverse prognostic factor for relapse (P = 0.037) and death (P = 0.05).
  
  
  CONCLUSIONS
  High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients. These findings need to be validated in larger cohorts.
authors: Second Department of Internal Medicine, Attikon University Hospital, Athens. diamando.psyrri@yale.edu
authors: A
authors: A
authors: Psyrri
authors: K T
authors: KT
authors: Kalogeras
authors: R
authors: R
authors: Kronenwett
authors: R M
authors: RM
authors: Wirtz
authors: A
authors: A
authors: Batistatou
authors: E
authors: E
authors: Bournakis
authors: E
authors: E
authors: Timotheadou
authors: H
authors: H
authors: Gogas
authors: G
authors: G
authors: Aravantinos
authors: C
authors: C
authors: Christodoulou
authors: T
authors: T
authors: Makatsoris
authors: H
authors: H
authors: Linardou
authors: D
authors: D
authors: Pectasides
authors: N
authors: N
authors: Pavlidis
authors: T
authors: T
authors: Economopoulos
authors: G
authors: G
authors: Fountzilas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D014158:Transcription, Genetic; D047368:Tumor Burden; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D003520:Cyclophosphamide; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes; D017239:Paclitaxel; D005472:Fluorouracil; D008727:Methotrexate