TY - JOUR
T1 - HER-2/neu gene amplification by Fluorescence In Situ Hybridization allows risk-group assessment in node-negative breast cancer
AU - Harbeck, Nadia
AU - Ross, Jeffrey S.
AU - Yurdseven, Suna
AU - Dettmar, Peer
AU - Pölcher, Martin
AU - Kuhn, Walther
AU - Ulm, Kurt
AU - Graeff, Henner
AU - Schmitt, Manfred
PY - 1999/4
Y1 - 1999/4
N2 - 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.
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.
KW - FISH
KW - Gene amplification
KW - HER-2/neu
KW - Node-negative breast cancer
KW - PAI-1
KW - Prognosis
KW - Protein ovcrcxpression
KW - Proto-oncogene c-erbB-2
KW - uPA
UR - http://www.scopus.com/inward/record.url?scp=0033109529&partnerID=8YFLogxK
U2 - 10.3892/ijo.14.4.663
DO - 10.3892/ijo.14.4.663
M3 - Article
C2 - 10087312
AN - SCOPUS:0033109529
SN - 1019-6439
VL - 14
SP - 663
EP - 671
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 4
ER -
