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HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.
- Source :
-
International journal of oncology [Int J Oncol] 1999 Apr; Vol. 14 (4), pp. 663-71. - Publication Year :
- 1999
-
Abstract
- 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Biomarkers, Tumor metabolism
Breast Neoplasms mortality
Breast Neoplasms pathology
Female
Gene Amplification
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lymphatic Metastasis
Middle Aged
Multivariate Analysis
Prognosis
Risk Assessment
Survival Analysis
Breast Neoplasms genetics
Receptor, ErbB-2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1019-6439
- Volume :
- 14
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 10087312
- Full Text :
- https://doi.org/10.3892/ijo.14.4.663