Rates of topoisomerase II-alpha and HER-2 gene amplification and expression in epithelial ovarian carcinoma.
OBJECTIVE
Topoisomerase II-alpha (T2a) is being actively investigated as a potential predictive marker of response to anthracyclines in breast cancer (BC). Although the role of T2a inhibitors as upfront and salvage treatment for epithelial ovarian carcinoma (EOC) remains unclear, we speculated that a small subgroup of ovarian cancer patients could derive a selective benefit from these agents. In this study, we investigated the actual rates of T2a and HER-2 amplification and overexpression by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively.


METHODS
Seventy-three samples of chemotherapy-naive patients with EOC were selected from our archives. FIGO stage and histology were available for most patients.


RESULTS
Based on arbitrary cut-offs of > or =1.5 and > or =2 (ratio copies/centromere17), amplification rates for HER-2 were 15/64 (23.4%) and 8/64 (12.5%) versus 16/64 (25%) and 5/64 (7.8%) for T2a. We found only 3/72 (4.2%) cases of HER-2 overexpression (3+) versus 15/70 (21.4%) for T2a (staining of >10% of the cells). There was a modest correlation between T2a amplification and overexpression (P=0.01) and a strong correlation between T2a and HER-2 amplification when these markers were analysed as continuous variables (P<0.001). T2a amplification significantly correlated with advanced FIGO stage (P=0.02).


CONCLUSIONS
The assessment of HER-2 and T2a amplification and overexpression by FISH and IHC, respectively, is feasible in EOC. These tests can be used for large-scale evaluation of the potential predictive and prognostic value of these markers in the future. Further studies with a special focus on T2a are needed to determine the best cut-offs for potential clinical use in the future.
Unité de Chimiothérapie, Institut Jules Bordet, Brussels, Belgium. max_mano@hotmail.com
M S
MS
Mano
A
A
Awada
A
A
Di Leo
V
V
Durbecq
M
M
Paesmans
F
F
Cardoso
D
D
Larsimont
M
M
Piccart
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016612:Paraffin Embedding; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases