title: Prognostic significance of RACGAP1 mRNA expression in high-risk early breast cancer: a study in primary tumors of breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial.
abstract: OBJECTIVE
  RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI).
  
  
  METHODS
  A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression.
  
  
  RESULTS
  High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank, p = 0.002) and OS (p < 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald's p = 0.008). High Ki67 protein expression was also an adverse prognostic factor for death (p = 0.016), while high NPI score values were not.
  
  
  CONCLUSIONS
  High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts.
authors.affiliation: Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, University of Athens School of Medicine, Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Pliarchopoulou
authors.forename: K T
authors.initials: KT
authors.lastname: Kalogeras
authors.forename: R
authors.initials: R
authors.lastname: Kronenwett
authors.forename: R M
authors.initials: RM
authors.lastname: Wirtz
authors.forename: A G
authors.initials: AG
authors.lastname: Eleftheraki
authors.forename: A
authors.initials: A
authors.lastname: Batistatou
authors.forename: M
authors.initials: M
authors.lastname: Bobos
authors.forename: N
authors.initials: N
authors.lastname: Soupos
authors.forename: G
authors.initials: G
authors.lastname: Polychronidou
authors.forename: H
authors.initials: H
authors.lastname: Gogas
authors.forename: E
authors.initials: E
authors.lastname: Samantas
authors.forename: C
authors.initials: C
authors.lastname: Christodoulou
authors.forename: T
authors.initials: T
authors.lastname: Makatsoris
authors.forename: N
authors.initials: N
authors.lastname: Pavlidis
authors.forename: D
authors.initials: D
authors.lastname: Pectasides
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult
chemical_list: D020690:GTPase-Activating Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; C115995:mgcRacGAP