PMID- 10087312
OWN - NLM
STAT- MEDLINE
DCOM- 19990528
LR  - 20190516
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 14
IP  - 4
DP  - 1999 Apr
TI  - HER-2/neu gene amplification by fluorescence in situ hybridization allows 
      risk-group assessment in node-negative breast cancer.
PG  - 663-71
AB  - In a collective of 112 node-negative breast cancer patients, we compared the 
      prognostic impact of HER-2/neu gene amplification (AMP) determined by 
      fluorescence in situ hybridization (FISH) and HER-2/neu protein overexpression 
      (EXP) measured by immunohistochemistry (IHC) with traditional prognostic factors 
      (tumor size, grade, steroid hormone receptor status, menopausal status) and tumor 
      invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor 
      PAI-1 determined by enzyme immunoassay (ELISA). Median follow-up in patients 
      still alive at time of analysis was 7 years. Automated FISH and IHC were 
      performed on parallel-cut formalin-fixed paraffin-embedded tissue sections. 
      HER-2/neu AMP was detected by FISH in 31% and HER-2/neu EXP was measured by IHC 
      in 41% of the cases. In 13% of the tumors, both AMP and EXP were found. FISH and 
      IHC results were concordant in 56% of all analyzed cases. In univariate analysis, 
      HER-2/neu AMP significantly predicted both disease-free (DFS) and overall 
      survival (OS). HER-2/neu EXP was significant for OS, only. In multivariate 
      analysis of all analyzed prognostic factors, HER-2/neu AMP was the only 
      independent predictive factor for both DFS and OS. CART analysis revealed that 
      HER-2/neu AMP together with the combination uPA/PAI-1 allowed optimal risk-group 
      assessment after a 7-year median follow-up: patients with low levels of both uPA 
      and PAI-1 and no HER-2/neu AMP had a significantly lower relapse rate (4.6%) than 
      the remaining patients (32%). In conclusion, HER-2/neu gene AMP determined by 
      FISH allowed a more accurate risk-group assessment than HER-2/neu protein EXP 
      measured by IHC. Combining the HER-2/neu gene status measured by FISH with levels 
      of tumor invasion markers uPA and PAI-1 improves clinically relevant risk-group 
      assessment. In addition to its prognostic strength, the significant impact of 
      HER-2/neu AMP on OS may reflect its ability to predict resistance to systemic 
      therapy.
FAU - Harbeck, N
AU  - Harbeck N
AD  - Frauenklinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat 
      Munchen, D-81675 Munich, Germany.
FAU - Ross, J S
AU  - Ross JS
FAU - Yurdseven, S
AU  - Yurdseven S
FAU - Dettmar, P
AU  - Dettmar P
FAU - Polcher, M
AU  - Polcher M
FAU - Kuhn, W
AU  - Kuhn W
FAU - Ulm, K
AU  - Ulm K
FAU - Graeff, H
AU  - Graeff H
FAU - Schmitt, M
AU  - Schmitt M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/metabolism
MH  - Breast Neoplasms/*genetics/mortality/pathology
MH  - Female
MH  - Gene Amplification
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphatic Metastasis
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Prognosis
MH  - Receptor, ErbB-2/*genetics
MH  - Risk Assessment
MH  - Survival Analysis
EDAT- 1999/03/24 00:00
MHDA- 1999/03/24 00:01
CRDT- 1999/03/24 00:00
PHST- 1999/03/24 00:00 [pubmed]
PHST- 1999/03/24 00:01 [medline]
PHST- 1999/03/24 00:00 [entrez]
AID - 10.3892/ijo.14.4.663 [doi]
PST - ppublish
SO  - Int J Oncol. 1999 Apr;14(4):663-71. doi: 10.3892/ijo.14.4.663.