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. © 2011 Japanese Cancer Association.