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Neoplasma Vol.53, p.393-401, 2006 |
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Title: Analysis of ERBB2 and TOP2A gene status using fluorescence in situ hybridization versus immunohistochemistry in localized breast cancer | ||
Author: K., BOUCHALOVA ; R., TROJANEC ; Z., KOLAR ; K., CWIERTKA ; I., CERNAKOVA ; V., MIHAL ; M., HAJDUCH ; | ||
Abstract: The aim of our study was to assess the ERBB2 and TOP2A gene status
in breast carcinoma tissue using fluorescence in
situ hybridization (FISH) and to compare their amplification with
immunohistochemistry assay (IHC) of the ERBB2, resp.
topoisomerase IIalpha proteins. TOP2A status is important in
tailored treatment as topoisomerase IIalpha is the molecular
target for
topoisomerase IIalpha inhibitors. This study was conducted to
determine whether the methods are equivalent in their assessment
of TOP2A status and to correlate the genetic findings with basic
tumor and disease characteristics.
Locus specific ERBB2, TOP2A genes and chromosome 17 centromeres
(CEP17) probes were hybridized to 72 formalin-
fixed paraffin-embedded (FFPE) tissue samples from patients with
non-metastatic breast carcinoma (M0). The ERBB2,
TOP2A and CEP17 signals were counted and gene numbers per nucleus
or per CEP17 were calculated, respectively. Sections
were also stained with commercial polyclonal antibody
(HercepTestTM), anti-topoisomerase IIalpha monoclonal antibody
(clone SWT3D1) and scored for the presence of membrane/nuclear
staining.
ERBB2 amplification was found in 20.3%, ERBB2 and TOP2A co-
amplification was detected in 14.5% of cases. Deletion
of the ERBB2/TOP2A gene was found in 1.4/2.8% of sections,
respectively. Concordance of FISH and IHC techniques
in the evaluation of ERBB2 and TOP2A status was found in 88.4% and
66.7%, respectively. The low concordance of FISH
versus IHC in the evaluation of TOP2A status was mainly due to the
presence of TOP2A amplified tumors in IHC negative
or weakly positive specimens. Topoisomerase IIalpha expression was
increased in bigger tumors, although direct correlation
with tumor grading was not found. ERBB2 amplification was found in
more aggressive breast cancers with grades 2 and 3,
respectively. Interestingly, chromosome 17 polysomy was more
frequently observed among older women ( >55 years), suffering
usually from less aggressive disease.
Our results confirm the high concordance of the ERBB2 and TOP2A
gene co-amplification in breast carcinoma. Differences
between FISH and IHC in the case of ERBB2 gene status were found
only in IHC 2+ sections as reported in the literature.
However, our study points to the importance of FISH examination of
TOP2A gene status in all tumors with ERBB2
amplification.
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Keywords: ERBB2, topoisomerase IIalpha, breast carcinoma, FISH, immunohistochemistry, anthracycline | ||
Year: 2006, Volume: 53, Issue: | Page From: 393, Page To: 401 | |
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