TY - JOUR
T1 - Combination of osteopontin and activated leukocyte cell adhesion molecule as potent prognostic discriminators in HER2- and ER-negative breast cancer
AU - Ihnen, M.
AU - Wirtz, R. M.
AU - Kalogeras, K. T.
AU - Milde-Langosch, K.
AU - Schmidt, M.
AU - Witzel, I.
AU - Eleftheraki, A. G.
AU - Papadimitriou, C.
AU - Jänicke, F.
AU - Briassoulis, E.
AU - Pectasides, D.
AU - Rody, A.
AU - Fountzilas, G.
AU - Müller, V.
PY - 2010/9/28
Y1 - 2010/9/28
N2 - 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 (N100, adjuvant treatment) and validation cohorts B (N200, no adjuvant treatment, low-risk) and C (N181, 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, P0.001, and OAS, P0.001. Although both validation cohorts showed diverse risk and treatment profiles, this marker constellation was concordantly associated with shorter DFS and OAS (P0.001 and P0.075 for cohort B and P0.043 and P0.001 for cohort C, respectively). In multivariate analysis, this algorithm was the main independent prognostic factor. Cohort B: DFS, P0.0065, OAS, not significant; cohort C: DFS, P0.026, OAS, P0.001.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.
AB - 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 (N100, adjuvant treatment) and validation cohorts B (N200, no adjuvant treatment, low-risk) and C (N181, 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, P0.001, and OAS, P0.001. Although both validation cohorts showed diverse risk and treatment profiles, this marker constellation was concordantly associated with shorter DFS and OAS (P0.001 and P0.075 for cohort B and P0.043 and P0.001 for cohort C, respectively). In multivariate analysis, this algorithm was the main independent prognostic factor. Cohort B: DFS, P0.0065, OAS, not significant; cohort C: DFS, P0.026, OAS, P0.001.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.
UR - http://www.scopus.com/inward/record.url?scp=77957237558&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6605840
DO - 10.1038/sj.bjc.6605840
M3 - Journal articles
C2 - 20736952
AN - SCOPUS:77957237558
SN - 0007-0920
VL - 103
SP - 1048
EP - 1056
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -
