title: Topoisomerase II alpha expression and the Ki-67 labeling index correlate with prognostic factors in estrogen receptor-positive and human epidermal growth factor type-2-negative breast cancer.
abstract: BACKGROUND
  Topoisomerase II alpha (Topo IIa) is involved in DNA replication and is a molecular target for anthracycline-based chemotherapy. The Ki-67 labeling index (LI) is an evaluation of tumor cell proliferation. The objective of this study was to evaluate relationships among Topo IIa expression, the Ki-67 LI, and prognostic factors in estrogen receptor (ER)-positive, human epidermal growth factor type-2 (HER2)-negative breast cancer.
  
  
  METHODS
  Seventy-one patients were diagnosed with ER-positive, HER2-negative breast cancer between July 2003 and December 2004. Formalin-fixed, paraffin-embedded tumor specimens were stained for Topo IIa expression and Ki-67 LI. We investigated the correlation of the level of Topo IIa expression and the Ki-67 LI with clinical factors such as age, tumor size, progesterone receptor status, nodal status, nuclear grade, and lymphovascular invasion (LVI).
  
  
  RESULTS
  Statistically significant differences were observed between Topo IIa overexpression, nuclear grade (p = 0.036), and LVI (p = 0.029). Topo IIa overexpression was statistically correlated with the Ki-67 LI (p < 0.0001). A statistically significant difference was observed between the Ki-67 LI and nuclear grade (p = 0.01). Survival analysis revealed the significant prognostic value of Ki-67 LI in patients with ER-positive, HER2-negative breast cancer (p = 0.003).
  
  
  CONCLUSIONS
  Ki-67 LI is a strong prognostic factor in ER-positive HER2-negative breast cancer. Topo IIa overexpression was significantly correlated with the Ki-67 LI, nuclear grade, and LVI. These findings suggest use of Topo IIa expression as a proliferation marker and a prognostic factor in ER-positive, HER2-negative breast cancer.
authors: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. tokiniwa@med.gunma-u.ac.jp
authors: Hideaki
authors: H
authors: Tokiniwa
authors: Jun
authors: J
authors: Horiguchi
authors: Daisuke
authors: D
authors: Takata
authors: Mami
authors: M
authors: Kikuchi
authors: Nana
authors: N
authors: Rokutanda
authors: Rin
authors: R
authors: Nagaoka
authors: Ayako
authors: A
authors: Sato
authors: Hiroki
authors: H
authors: Odawara
authors: Katsunori
authors: K
authors: Tozuka
authors: Tetsunari
authors: T
authors: Oyama
authors: Izumi
authors: I
authors: Takeyoshi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human