HER-2, TOP2A and Chromosome 17 Alterations in Breast Cancer

Asli Rehber BESER1, Sitki TUZLALI2, Deniz GUZEY3, Semra DOLEK GULER4, Seniha HACIHANEFIOGLU5, Nejat DALAY1

1Department of Basic Oncology, Istanbul University Oncology Institute, Istanbul, Turkey
2Department of Pathology, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey
3Department of Surgery, Vakif Gureba Hospital, Istanbul, Turkey
4Department of Clinical Oncology, Istanbul University Oncology Institute, Istanbul, Turkey
5Department of Medical Biology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey


HER-2 amplification is a biomarker for identifying patients who respond to trastuzumab and has been evaluated as a factor predicting the response to anthracyclines. The relationship between HER-2 and response to anthracycline therapy may also be the result of the close localization of TOP2A on 17q. It has been a matter of debate whether these two genes, HER-2 and TOP2A, behave separately on different amplicons or act together thus making it possible to predict the TOP2A status from the HER-2 status. In this study TOP2A, HER-2 and chromosome 17 aneusomy were investigated by fluorescent in situ hybridization (FISH) in 50 consecutive breast cancer patients. HER-2 amplification was detected in 11 patients (22%) and TOP2A changes were seen in 6 patients (12%); two amplifications and two deletions were observed in HER-2-amplified cases and two deletions in HER-2-nonamplified cases. Three of the TOP2A-deleted cases had polysomy 17. HER-2 copy number was higher than the TOP2A copy number in one patient with co-amplification. Polysomy was observed in 9 cases (18%) and monosomy in 6 cases (12%). Aneusomy was the sole anomaly in 11 patients (22%). We conclude that the TOP2A status cannot be predicted from the HER-2 status and evaluation of the TOP2A status only in patients with HER-2 overexpression may lead to missing cases with TOP2A deletion with possible resistance to therapy. Other factors modulating topo II activity may also affect the response to therapy. Studies evaluating different parameters that can modulate topo II activity and the response to the drugs targeting the enzyme are necessary. Pathology & Oncology Research, Vol 13, Nr 3, 180-185, 2007

Key words: TOP2A; HER-2; breast cancer

Received: Oct 17, 2006; accepted: Sep 5, 2007
Correspondence: Nejat DALAY, Department of Basic Oncology, Istanbul University Oncology Institute, Istanbul 34093, Turkey; Tel: 90212 4142434, Fax: 90212 5348078; E-mail:

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