title: Glutaminase expression is a poor prognostic factor in node-positive triple-negative breast cancer patients with a high level of tumor-infiltrating lymphocytes.
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.
authors.affiliation: Department of Pathology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.|Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Heo
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.|Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Seul Ki
authors.initials: SK
authors.lastname: Choi
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Song
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.|Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.|Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Hye Seon
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.|Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Suk Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.|Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Won Seon
authors.initials: WS
authors.lastname: Bang
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. backlila@gmail.com.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D005972:Glutaminase / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D005972:Glutaminase
keywords: Glutaminase; Prognosis; Triple-negative breast cancer; Tumor-infiltrating lymphocytes