Kim Joo Young, Heo Sun-Hee, Choi Seul Ki, Song In Hye, Park In Ah, Kim Young-Ae, Park Hye Seon, Park Suk Young, Bang Won Seon, Gong Gyungyub, Lee Hee Jin
Department of Pathology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
Virchows Arch. 2017 Apr;470(4):381-389. doi: 10.1007/s00428-017-2083-5. Epub 2017 Feb 9.
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.
谷氨酰胺代谢正成为肿瘤代谢失调的一个方面。三阴性乳腺癌（TNBC）细胞依赖谷氨酰胺，而管腔型细胞往往不依赖谷氨酰胺。因此，TNBC患者可能从针对谷氨酰胺代谢的治疗中获益。为了研究谷氨酰胺代谢的临床意义，我们检测了TNBC中肿瘤细胞和肿瘤浸润淋巴细胞（TIL）中谷氨酰胺酶的表达及其预后意义。我们收集了658例手术切除的TNBC病例，通过免疫组织化学染色分析肿瘤细胞和TIL中谷氨酰胺酶的表达。在237例（36.0%）肿瘤细胞和104例（15.5%）TIL中观察到谷氨酰胺酶表达。虽然肿瘤细胞中谷氨酰胺酶表达与低水平的TIL显著相关（p = 0.018），但在TIL水平高的病例中，TIL中谷氨酰胺酶表达显著更高（p = 0.031）。肿瘤细胞中谷氨酰胺酶表达与有淋巴结转移且TIL水平高的患者无病生存期差显著相关（p = 0.020）。此外，它是一个独立的不良预后因素（风险比 = 10.643，95%置信区间 = 1.999 - 56.668；p = 0.006）。在一部分TNBC患者的肿瘤细胞中观察到谷氨酰胺酶表达。它与有淋巴结转移且TIL水平高的TNBC中低水平的TIL和无病生存期差显著相关。
