scholarly journals Prognostic values of L-type amino acid transporter 1 and CD98hc expression in breast cancer

2020 ◽  
pp. jclinpath-2020-206457
Author(s):  
Masaaki Ichinoe ◽  
Tetuo Mikami ◽  
Nobuyuki Yanagisawa ◽  
Tsutomu Yoshida ◽  
Kiyomi Hana ◽  
...  

AimsL-type amino acid transporter 1 (LAT1) is a major Na+-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.MethodsLAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.ResultsHigh levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.ConclusionsLAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.

2021 ◽  
Author(s):  
Sasagu Kurouzmi ◽  
Kyoichi Kaira ◽  
Hiroshi Matsumoto ◽  
Masafumi Kurosumi ◽  
Takehiko Yokobori ◽  
...  

Abstract PURPOSE: L-type amino acid transporter 1 (LAT1), also referred to as SLC7A5, is believed to regulate tumor metabolism and be associated with tumor proliferation. In invasive breast cancer, we clinicopathologically investigated the utility of LAT1 expression. METHODS: LAT1 expression was evaluated via immunohistochemistry analyses in 250 breast cancer patients undergoing long-term follow-up. We assessed the relationship between LAT1 expression and the patients’ outcomes and clinicopathological factors. Breast cancer-specific survival stratified by LAT1 expression was assessed.RESULTS: High LAT1 expression was significantly correlated with estrogen receptor (ER) negativity, progesterone receptor negativity, high histological grade, increased tumor-infiltrating lymphocytes, and programmed death ligand 1 positivity. Among the ER-positive and human epidermal growth factor 2-negative type cases, high LAT1 was an independent indicator of poor outcomes (hazard ratio (HR) = 2.97; 95% confidence interval (CI), 1.16–7.62; p = 0.023). Moreover, high LAT1 expression was an independent poor prognostic factor in luminal B-like breast cancer with aggressive features (HR = 3.39; 95% CI, 1.35–8.52; p = 0.0094).CONCLUSIONS: High LAT1 expression identified a subgroup of invasive breast cancer characterized by aggressive behavior and high tumor immunoreaction. Our findings suggest that LAT1 might be a candidate therapeutic target for breast cancer patients, particularly those with luminal B-like type breast cancer.


2015 ◽  
Vol 469 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Ellappan Babu ◽  
Yangzom D. Bhutia ◽  
Sabarish Ramachandran ◽  
Jaya P. Gnanaprakasam ◽  
Puttur D. Prasad ◽  
...  

Deletion of the amino acid transporter Slc6a14 in mice suppresses tumour growth in spontaneous models of breast cancer via interference with mammalian target of rapamycin (mTOR) pathway; this indicates an obligatory role for SLC6A14 in breast cancer, highlighting its potential as a therapeutic target.


2011 ◽  
Vol 103 (2) ◽  
pp. 382-389 ◽  
Author(s):  
Mio Furuya ◽  
Jun Horiguchi ◽  
Hiroki Nakajima ◽  
Yoshikatsu Kanai ◽  
Tetsunari Oyama

2010 ◽  
Vol 45 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Zhongxing Liang ◽  
Heidi T. Cho ◽  
Larry Williams ◽  
Aizhi Zhu ◽  
Ke Liang ◽  
...  

2012 ◽  
Vol 136 (9) ◽  
pp. 993-1000 ◽  
Author(s):  
Stella Petroni ◽  
Teresa Addati ◽  
Eliseo Mattioli ◽  
Maria Angela Caponio ◽  
Carmela Quero ◽  
...  

Context.—Chromosome 17 polysomy has been identified in 5% to 50% of invasive breast cancers; even though a relationship with human epidermal growth factor receptor 2 (HER2/neu) status has been reported, other studies have shown that coincident centromere 17 (Cep17) amplification may be the cause of an overestimation of chromosome 17 polysomy in fluorescence in situ hybridization (FISH) testing. Objective.—To evaluate polysomy/amplification of Cep17 in invasive breast cancer with relation to proliferative activity (Ki-67), estrogen receptor, progesterone receptor, and HER2/neu status, in an attempt to identify a subgroup of patients with a worse prognosis. Design.—A total of 647 cases of invasive ductal breast cancer were collected and subjected to FISH analysis for HER2/neu gene and centromere 17 alteration, HercepTest for HER2/neu protein expression, and routine immunohistochemistry for Ki-67 and hormone receptor status. Results.—Copy number gain of Cep17 was observed in 27.3% of cases. Within this group, HER2/neu gene amplification was detected in 14.1% of cases, whereas HER2/neu expression was scored 3+ in 20.1% of cases; about half of the HER2/neu overexpressing cases (9.8%) did not show amplification by FISH. Moreover, 69% of polysomic cases showed high Ki-67 index. Conclusions.—(1) Centromere 17–altered cases are frequently HER2/neu overexpressing but not amplified, resulting in HercepTest/FISH disagreement; (2) HER2/neu amplification is seen at a higher incidence in cases without Cep17 copy number alterations, which are therefore not necessarily due to chromosome 17 disorder; (3) proliferation index is significantly higher in aneusomic tumors. These data suggest that the presence of Cep17 alterations could identify a subset of breast cancers with more aggressive biological and clinical behavior, which may show nonresponsiveness to conventional therapy independently of HER2/neu amplification status.


2010 ◽  
Vol 31 (8) ◽  
pp. 699-707 ◽  
Author(s):  
Fan-Lin Kong ◽  
YinHan Zhang ◽  
Mohammad S. Ali ◽  
Chanksok Oh ◽  
Richard Mendez ◽  
...  

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