Correlation of L-type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis.

Abstract

Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98- (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC.

• Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari Oyama
• Journal: Cancer science (Cancer Sci) Vol. 103 Issue 2 Pg. 382-9 (Feb 2012) ISSN: 1349-7006 [Electronic] England
• PMID: 22077314 (Publication Type: Journal Article)
• Copyright: © 2011 Japanese Cancer Association.

Chemical References

• Biomarkers, Tumor
• Fusion Regulatory Protein-1
• Large Neutral Amino Acid-Transporter 1
• Receptors, Estrogen
• Receptors, Progesterone
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (metabolism)
• Cell Proliferation
• Disease Progression
• Female
• Fusion Regulatory Protein-1 (biosynthesis, metabolism)
• Humans
• Large Neutral Amino Acid-Transporter 1 (biosynthesis, metabolism)
• Middle Aged
• Prognosis
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Risk Factors
• Survival Rate