Does Gene Amplification Correlate With Protein Expression When Detecting Topisomerase 11a in Breast Cancer a Comparison using Immunohistochemistry and Fluorescent in situ Hybridisation (FISH)

Written by Craig Webster on .

Gavin Rock, Cellular Pathology

Background; Topoisomersase IIα (TOPO IIα) is a key enzyme in the DNA replication process and is one of the targets for anthracyclines, a chemotherapeutic agent.  The TOPO IIα gene is located in close proximity to the HER2 gene on chromosome 17q21, which is a marker of a poor prognostic group of breast tumours.  While the effects of TOPO IIα protein expression and gene copy number levels are being investigated for their response to treatment, the laboratory tests for TOPO IIα are yet to be clarified.

Aims; This study set out to test the correlation between TOPO IIα protein expression and its gene ratio to identify if the HER2 system of testing, where gene amplification almost always leads to overexpression, could potentially be applied to TOPO IIα.

Results; TOPO IIα€™s protein expression did not correlate with its gene amplification ratio (Spearmans 0.230, p=0.142).  However, all the cases that showed gene amplification (>2.00), also exhibited protein expression (‰¥10%), but there were a subset of cases that showed overexpression but displayed a normal gene ratio.  A further find of this study was that all TOPO IIα gene abnormalities, amplification and deletions, were only found in the HER2 positive group of tumours.

Conclusion; TOPO IIα gene amplification and protein expression was found not to correlate in this study and therefore applying the HER2 method of testing would make the investigations less robust.  Furthermore, due to TOPO IIα gene amplification accounting for only one quarter of all overexpressed cases (‰¥10%), FISH alone may be too restrictive to identify all the cases that might benefit from anthracycline treatment.  However, the expression of TOPO IIα involves complex pathways and may be the subject of other factors (proliferation rate, p53 status).  Therefore, if it proves that response to treatment is best identified by TOPO IIα gene ratio then FISH alone would be sufficient.