title: 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.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. mio-k@med.gunma-u.ac.jp
authors.forename: Mio
authors.initials: M
authors.lastname: Furuya
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D027261:Fusion Regulatory Protein-1 / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D027261:Fusion Regulatory Protein-1; D027283:Large Neutral Amino Acid-Transporter 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human