title: HOXB9 expression promoting tumor cell proliferation and angiogenesis is associated with clinical outcomes in breast cancer patients.
abstract: BACKGROUND
  Studies have suggested that HOXB9 expression in breast cancer cells promotes cellular invasiveness, metastatic ability, and tumor neovascularization in the surrounding tissue in in vitro and in vivo assays. These findings imply that HOXB9 overexpression may alter tumor-specific cell fates and the tumor stromal microenvironment, contributing to breast cancer progression. The objective of this study was to analyze whether these results could be applied to clinical practice.
  
  
  METHODS
  A total of 141 consecutive, invasive ductal carcinoma patients who underwent surgical treatment were examined. Immunohistochemical staining was performed to evaluate the expression of HOXB9, Ki-67, CD31, and CD34, and the association of tumor proliferation and angiogenesis with HOXB9 expression was analyzed.
  
  
  RESULTS
  Of the 141 tumor specimens immunostained for HOXB9, 69 (48.9%) stained positive. Larger primary tumor size, hormone receptor negativity, HER2 positivity, higher nuclear grade, and number of pathologic nodal metastases were significant variables associated with HOXB9 expression. Notably, 12 (92.3%) of 13 triple-negative breast cancer cases showed HOXB9 expression. Disease-free survival and overall survival were significantly different between the HOXB9-positive and HOXB9-negative groups (hazard ratio 20.714, P = 0.001; and hazard ratio 9.206, P = 0.003, respectively). Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for disease-free survival (hazard ratio 15.532, P = 0.009). HOXB9-positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio compared with HOXB9-negative tumors.
  
  
  CONCLUSIONS
  HOXB9 expression, which promotes tumor proliferation and angiogenesis, is a significant prognostic factor in breast cancer.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Seki
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hayashida
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Jinno
authors.forename: Shigemichi
authors.initials: S
authors.lastname: Hirose
authors.forename: Michio
authors.initials: M
authors.lastname: Sakata
authors.forename: Maiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shyamala
authors.initials: S
authors.lastname: Maheswaran
authors.forename: Makio
authors.initials: M
authors.lastname: Mukai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D015996:Survival Rate
chemical_list: C491257:HOXB9 protein, human; D018398:Homeodomain Proteins