title: Combination of osteopontin and activated leukocyte cell adhesion molecule as potent prognostic discriminators in HER2- and ER-negative breast cancer.
abstract: BACKGROUND
  To analyse the discriminative impact of osteopontin (OPN) and activated leukocyte cell adhesion molecule (ALCAM), combined with human epidermal growth factor 2 (HER2) and oestrogen receptor (ER) in breast cancer.
  
  
  METHODS
  Osteopontin, ALCAM, HER2 and ER mRNA expression in breast cancer tissues of 481 patients were analysed (mRNA microarray analysis, kinetic RT-PCR). Hierarchical clustering was performed in training cohort A (N=100, adjuvant treatment) and validation cohorts B (N=200, no adjuvant treatment, low-risk) and C (N=181, adjuvant treatment, high-risk).
  
  
  RESULTS
  Negative/low ER and HER2, high OPN and low ALCAM mRNA expression helped to identify patients at particularly high risk, showing shorter DFS, P<0.001, and OAS, P=0.001. Although both validation cohorts showed diverse risk and treatment profiles, this marker constellation was concordantly associated with shorter DFS and OAS (P<0.001 and P=0.075 for cohort B and P=0.043 and P<0.001 for cohort C, respectively). In multivariate analysis, this algorithm was the main independent prognostic factor. Cohort B: DFS, P=0.0065, OAS, not significant; cohort C: DFS, P=0.026, OAS, P<0.001.
  
  
  CONCLUSIONS
  Activated leukocyte cell adhesion molecule and OPN mRNA expression has a strong discriminative impact on survival within cancer patients with low or negative expression of ER and HER2, so called 'high-risk' breast cancers, and might help in identifying patients who could benefit from new treatment approaches like targeted therapies in the adjuvant setting.
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg D-20246, Germany. m.ihnen@uke.uni-hamburg.de
authors.forename: M
authors.initials: M
authors.lastname: Ihnen
authors.forename: R M
authors.initials: RM
authors.lastname: Wirtz
authors.forename: K T
authors.initials: KT
authors.lastname: Kalogeras
authors.forename: K
authors.initials: K
authors.lastname: Milde-Langosch
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: I
authors.initials: I
authors.lastname: Witzel
authors.forename: A G
authors.initials: AG
authors.lastname: Eleftheraki
authors.forename: C
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: F
authors.initials: F
authors.lastname: Jänicke
authors.forename: E
authors.initials: E
authors.lastname: Briassoulis
authors.forename: D
authors.initials: D
authors.lastname: Pectasides
authors.forename: A
authors.initials: A
authors.lastname: Rody
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
authors.forename: V
authors.initials: V
authors.lastname: Müller
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D016000:Cluster Analysis; D003663:Decision Trees; D018572:Disease-Free Survival; D039621:Eukaryotic Initiation Factor-3; D005260:Female; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D012306:Risk
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D039621:Eukaryotic Initiation Factor-3; D053495:Osteopontin; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C105988:EIF3A protein, human