title: Topoisomerase II-alpha gene deletion is not frequent as its amplification in breast cancer.
abstract: Topoisomerase II-alpha (TOP2A) has been investigated as a potential predictor for the response to doxorubicin-based chemotherapy which is a representative TOP2A inhibitor and one of the most effective chemotherapeutics for the breast cancer treatment. We performed the assay for the TOP2A gene amplification and deletion on a tissue microarray (TMA) of 284 breast tumor samples from the patients treated by doxorubicin-based adjuvant chemotherapy. TOP2A gene was deleted in six patients (2.1%), whereas TOP2A gene was amplified in 20 (7.1%) of 284 tumors. Twenty-four of 26 TOP2A amplifications and deletions were associated with HER2 co-amplification. TOP2A amplification or deletion was not associated with poor clinical outcome. Nine (34.6%) of 26 patients with TOP2A amplification or deletion had recurrent disease. Thirty percent of the patients with TOP2A amplification had systemic recurrence whereas 50% of the patients with TOP2A deletion had systemic recurrence. On multivariate analysis, histologic grade and tumor size were the significant predictors for the disease-free survival and histologic grade was an only significant predictor for the overall survival. Our study indicates that response to the doxorubicin-based chemotherapy might be stratified by TOP2A amplification and deletion. However, relative low frequency of TOP2A genetic changes seems to hamper its clinical utility.
authors.affiliation: Department of Pathology, Inje University Sanggye Paik Hospital, 761-1, Sanggye-dong, Nowon-gu, 139-707, Seoul, South Korea.
authors.forename: Kyeongmee
authors.initials: K
authors.lastname: Park
authors.forename: Sehwan
authors.initials: S
authors.lastname: Han
authors.forename: Geum-Hee
authors.initials: GH
authors.lastname: Gwak
authors.forename: Huyn-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jungyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D015999:Multivariate Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D013997:Time Factors
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human