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Virchows Archiv

, Volume 470, Issue 4, pp 381–389 | Cite as

Glutaminase expression is a poor prognostic factor in node-positive triple-negative breast cancer patients with a high level of tumor-infiltrating lymphocytes

  • Joo Young Kim
  • Sun-Hee Heo
  • Seul Ki Choi
  • In Hye Song
  • In Ah Park
  • Young-Ae Kim
  • Hye Seon Park
  • Suk Young Park
  • Won Seon Bang
  • Gyungyub Gong
  • Hee Jin LeeEmail author
Original Article

Abstract

Glutamine metabolism is emerging as one aspect of dysregulated metabolism of tumors. Triple-negative breast cancer (TNBC) cells are glutamine dependent, whereas luminal-type cells tend to be glutamine independent. Therefore, TNBC patients might benefit from therapies targeting glutamine metabolism. To investigate the clinical significance of glutamine metabolism, we examined expression and prognostic significance of glutaminase in tumor cells and tumor-infiltrating lymphocytes (TILs) in TNBC. We retrieved 658 surgically resected TNBCs and analyzed glutaminase expression in tumor cells and TILs by immunohistochemical staining. Glutaminase expression was observed in 237 cases (36.0%) in tumor cells and 104 cases (15.5%) in TILs. Although glutaminase expression in tumor cells was significantly associated with a low level of TILs (p = 0.018), glutaminase expression in TILs was significantly higher in cases with a high level of TILs (p = 0.031). Glutaminase expression in tumor cells was significantly associated with poor disease-free survival in patients with lymph node metastasis and high levels of TILs (p = 0.020). In addition, it was an independent poor prognostic factor (hazard ratio = 10.643, 95% confidence interval = 1.999–56.668; p = 0.006). Glutaminase expression in tumor cells was observed in a subset of TNBC patients. It was significantly associated with a low level of TILs and poor disease-free survival in TNBCs presenting with lymph node metastasis and high levels of TILs.

Keywords

Glutaminase Tumor-infiltrating lymphocytes Triple-negative breast cancer Prognosis 

Notes

Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A02036484) and the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (2016-732).

Compliance with ethical standards

This study was approved by the Institutional Review Board of Asan Medical Center and confirmed to the provisions of the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Joo Young Kim
    • 1
  • Sun-Hee Heo
    • 2
    • 3
  • Seul Ki Choi
    • 2
    • 3
  • In Hye Song
    • 2
  • In Ah Park
    • 2
  • Young-Ae Kim
    • 2
    • 3
  • Hye Seon Park
    • 2
    • 3
  • Suk Young Park
    • 2
    • 3
  • Won Seon Bang
    • 2
    • 3
  • Gyungyub Gong
    • 2
  • Hee Jin Lee
    • 2
    Email author
  1. 1.Department of PathologyKorea University Anam Hospital, Korea University College of MedicineSeoulSouth Korea
  2. 2.Department of PathologyUniversity of Ulsan College of Medicine, Asan Medical CenterSeoulSouth Korea
  3. 3.Asan Center for Cancer Genome Discovery, Asan Institute for Life SciencesUniversity of Ulsan College of Medicine, Asan Medical CenterSeoulSouth Korea

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