TOP2A/CEP17 pin

FISH

TOP2A/CEP17

Alternate Test Names:
TOP2A

Methodology: FISH

Clinical Significance:
Topoisomerase II-α (TOP2A) fluorescence in situ hybridization (FISH) is used for evaluation of TOP2A gene amplification and/or deletion in some cancers. Topoisomerase II is located near the HER2 (ERBB2) gene on chromosome 17. A significant subset (~30-40%) of breast cancer patients who show HER2 gene overexpression by FISH show gene amplification and/or deletion of TOP2A. Since adriamycin-based therapies limit cell growth by targeting TOP2A, identifying patients showing TOP2A gene amplification may help to identify those patients who may benefit from adriamycin-based therapies. In addition, deletion of TOP2A has also been associated with response to adriamycin-based therapies.

Chemotherapies incorporating anthracyclines (daunorubicin, doxorubicin, and epirubicin), which are thought to act through the enzyme TOP2A in cancer cells, are commonly employed in the treatment of breast cancer. Since benefit from anthracycline-based adjuvant chemotherapy may be restricted to a subgroup of patients, a method of identifying these patients has long been sought. In the past, HER2 gene amplification (by FISH) and protein overexpression (by IHC) have been associated with anthracycline sensitivity, and it has been hypothesized that in such patients the HER2 biomarker represents a surrogate marker for amplification of the TOP2A gene present in the same region of chromosome 17. Promising evidence and strong corroboration of this hypothesis has been presented recently. Investigators recently found that TOP2A was co-amplified in 37% of HER2-amplified breast cancers, and only those HER2 amplified patients with concomitant TOP2A gene amplification showed improved overall survival from individually tailored and dose-escalated, anthracycline-based adjuvant chemotherapy. In the former study, published by the Danish Breast Cancer Cooperative Group, investigators found that patients with TOP2A gene amplification had significantly increased recurrence-free and overall survival when treated with anthracycline-based chemotherapy; in this study, however, a nearly identical hazard ratio was found in patients with either TOP2A deletions or TOP2A gene amplification. Thus, TOP2A gene amplification and deletion may predict response to anthracycline-containing breast chemotherapy, suggesting that TOP2A FISH studies may play a promising role as a predictive marker of tumor sensitivity to these drugs.

Probe type: Dual color enumeration

Organ: Breast

Disease State: Adenocarcinoma, Breast Cancer

CPT Code(s): 88374 (reference only; CPTs may vary)

Turnaround Time: Within 3-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements:
• Formalin-fixed, paraffin-embedded tissue block or cell block - OR -
• Minimum of 5 unstained slide cut at 4µm for each test requested