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Breast Cancer Research and Treatment

, Volume 123, Issue 3, pp 733–745 | Cite as

Expression pattern of stromal cell-derived factor-1 chemokine in invasive breast cancer is correlated with estrogen receptor status and patient prognosis

  • Takayuki Kobayashi
  • Hitoshi TsudaEmail author
  • Tomoyuki Moriya
  • Tamio Yamasaki
  • Ryoko Kikuchi
  • Shigeto Ueda
  • Jiro Omata
  • Junji Yamamoto
  • Osamu Matsubara
Preclinical study

Abstract

Chemokine receptor CXCR4 is known to be crucially involved in tumor progression, but the role of its ligand, stromal cell-derived factor-1 (SDF-1), remains unclear. The present study was conducted to clarify the clinicopathological and prognostic impact of SDF-1 expression in invasive breast cancers. Expression of SDF-1 mRNA and protein was examined in five breast cancer cell lines with or without estradiol treatment. In 52 surgically resected breast cancers, the level of SDF-1 mRNA in frozen samples and the pattern of SDF-1 protein immunoreactivity in formalin-fixed paraffin-embedded tissue sections were compared. In another cohort of 223 breast cancers, the correlation between SDF-1 immunoreactivity and clinicopathological parameters was examined using a tissue microarray. Estradiol treatment markedly increased the expression of SDF-1 mRNA and protein in the estrogen receptor (ER)-positive cell lines, MCF-7 and T47D. Among the 52 resected breast cancers, those with a cytoplasmic-dominant pattern of SDF-1 expression showed higher SDF-1 mRNA levels (median 27.4) than those with a membrane-dominant or negative pattern (median 13.6, P = 0.0017). Accordingly, the cytoplasmic-dominant pattern was defined as “high SDF-1 expression,” and other patterns were defined as “low SDF-1 expression.” Among the cohort of 223 tumors, “high SDF-1 expression” was detected in 158 (70.9%) and was significantly correlated with ER positivity (P < 0.0001), HER2 negativity (P = 0.021), and lower grade (P < 0.0001). Univariate analysis demonstrated that “high SDF-1 expression” was a significant indicator of better clinical outcome in both the entire patient cohort (P = 0.017) and the 133 patients with ER-positive tumors (P = 0.036), but not in the 90 patients with ER-negative tumors. Multivariate analysis showed that SDF-1 status was an independent factor related to overall survival in patients with ER-positive tumors (P = 0.046). SDF-1 status is a significant prognostic factor and may be clinically useful for assigning adjuvant therapy to patients with ER-positive invasive breast cancers.

Keywords

SDF-1 (CXCL12) Breast cancer Estrogen receptor Estrogen-regulated genes Immunohistochemistry 

Abbreviations

SDF-1

Stromal cell-derived factor-1

ERG

Estrogen-regulated gene

TMA

Tissue microarray

ER

Estrogen receptor alpha

PR

Progesterone receptor

Notes

Acknowledgments

We thank Dr. Yumi Miyazaki and Ms. Kozue Suzuki for technical assistance and Dr. Keiichi Iwaya for helpful discussion. This work was supported by grants from the Ministry of Defense, Japan, the Ministry of Health, Labor, and Welfare, Japan, the Princess Takamatsu Cancer Research Fund, and the Foundation for Promotion of Defense Medicine.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Takayuki Kobayashi
    • 1
  • Hitoshi Tsuda
    • 1
    • 4
    Email author
  • Tomoyuki Moriya
    • 2
  • Tamio Yamasaki
    • 3
  • Ryoko Kikuchi
    • 1
  • Shigeto Ueda
    • 2
  • Jiro Omata
    • 2
  • Junji Yamamoto
    • 2
  • Osamu Matsubara
    • 1
  1. 1.Department of Basic PathologyNational Defense Medical CollegeTokorozawa, SaitamaJapan
  2. 2.Department of SurgeryNational Defense Medical CollegeTokorozawa, SaitamaJapan
  3. 3.Department of General MedicineNational Defense Medical CollegeTokorozawa, SaitamaJapan
  4. 4.Pathology Section, Clinical Laboratory DivisionNational Cancer Center HospitalChuo-ku, TokyoJapan

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