Annals of Surgical Oncology

, Volume 19, Issue 6, pp 1831–1840 | Cite as

HOXB9 Expression Promoting Tumor Cell Proliferation and Angiogenesis Is Associated with Clinical Outcomes in Breast Cancer Patients

  • Hirohito Seki
  • Tetsu Hayashida
  • Hiromitsu Jinno
  • Shigemichi Hirose
  • Michio Sakata
  • Maiko Takahashi
  • Shyamala Maheswaran
  • Makio Mukai
  • Yuko Kitagawa
Breast Oncology



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.


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.


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.


HOXB9 expression, which promotes tumor proliferation and angiogenesis, is a significant prognostic factor in breast cancer.


Breast Cancer Overall Survival High Nuclear Grade Intratumoral Microvessel Density HOXB9 Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Chisato Saito, Hiroshi Okazaki, and Kazuhiro Miyao for their technical support and helpful discussions. This research was supported by the Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research [B] (21791260 and 23791499 to T.H.) and [C] (22591442 to H.J., 21591677 to M.T.), and a Grant-in-Aid from the Global Center of Excellence Program entitled “Education and Research Center for Stem Cell Medicine” (Keio University).

Supplementary material

10434_2012_2295_MOESM1_ESM.pdf (267 kb)
Supplementary material 1 (PDF 267 kb)


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Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Hirohito Seki
    • 1
  • Tetsu Hayashida
    • 1
  • Hiromitsu Jinno
    • 1
  • Shigemichi Hirose
    • 2
  • Michio Sakata
    • 1
  • Maiko Takahashi
    • 1
  • Shyamala Maheswaran
    • 3
  • Makio Mukai
    • 2
  • Yuko Kitagawa
    • 1
  1. 1.Department of SurgeryKeio University School of MedicineTokyoJapan
  2. 2.Division of Diagnostic PathologyKeio University School of MedicineTokyoJapan
  3. 3.Department of SurgeryMassachusetts General Hospital and Harvard Medical SchoolCharlestownUSA

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