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

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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.

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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).

Author information

Correspondence to Hee Jin Lee.

Ethics declarations

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.

Additional information

Joo Young Kim and Sun-Hee Heo contributed equally to this article.

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Cite this article

Kim, J.Y., Heo, S., Choi, S.K. et al. Glutaminase expression is a poor prognostic factor in node-positive triple-negative breast cancer patients with a high level of tumor-infiltrating lymphocytes. Virchows Arch 470, 381–389 (2017). https://doi.org/10.1007/s00428-017-2083-5

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Keywords

  • Glutaminase
  • Tumor-infiltrating lymphocytes
  • Triple-negative breast cancer
  • Prognosis