Combination of osteopontin and activated leukocyte cell adhesion molecule as potent prognostic discriminators in HER2- and ER-negative breast cancer

Br J Cancer. 2010 Sep 28;103(7):1048-56. doi: 10.1038/sj.bjc.6605840. Epub 2010 Aug 24.


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.

Conclusion: 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.

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / genetics*
  • Adult
  • Aged
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Cluster Analysis
  • Decision Trees
  • Disease-Free Survival
  • Eukaryotic Initiation Factor-3
  • Female
  • Humans
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Osteopontin / genetics*
  • Prognosis
  • RNA, Messenger / metabolism
  • Receptor, ErbB-2 / genetics*
  • Receptors, Estrogen / genetics*
  • Risk


  • Activated-Leukocyte Cell Adhesion Molecule
  • EIF3A protein, human
  • Eukaryotic Initiation Factor-3
  • RNA, Messenger
  • Receptors, Estrogen
  • Osteopontin
  • Receptor, ErbB-2