Clinical significance of coexpression of L-type amino acid transporter 1 (LAT1) and ASC amino acid transporter 2 (ASCT2) in lung adenocarcinoma.
BACKGROUND
L-type amino acid transporter 1 (LAT1) and ASC amino acid transporter 2 (ASCT2) have been associated with tumor growth and progression. However, the clinical significance of LAT1 and ASCT2 coexpression in the prognosis of patients with lung adenocarcinoma remains unclear.


METHODS
In total, 222 patients with surgically resected lung adenocarcinoma were investigated retrospectively. Tumor sections were stained immunohistochemically for LAT1, ASCT2, CD98, phosphorylated mammalian target-of-rapamycin (p-mTOR), and Ki-67, and microvessel density (MVD) was determined by staining for CD34. Epidermal growth factor receptor (EGFR) mutation status was also examined.


RESULTS
LAT1 and ASCT2 were positively expressed in 22% and 40% of cases, respectively. Coexpression of LAT1 and ASCT2 was observed in 12% of cases and was associated significantly with disease stage, lymphatic permeation, vascular invasion, CD98, Ki-67, and p-mTOR. Only LAT1 and ASCT2 coexpression indicated a poor prognosis for lung adenocarcinoma. Furthermore, this characteristic was recognized in early-stage patients, especially those who had wild-type, rather than mutated, EGFR. Multivariate analysis confirmed that the coexpression of LAT1 and ASCT2 was an independent factor for predicting poor outcome.


CONCLUSIONS
LAT1 and ASCT2 coexpression is an independent prognostic factor for patients with lung adenocarcinoma, especially during the early stages, expressing wild-type EGFR.
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Tomohiro
T
Yazawa
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Kimihiro
K
Shimizu
Department of Oncology Clinical Development, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Kyoichi
K
Kaira
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Toshiteru
T
Nagashima
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Yoichi
Y
Ohtaki
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Jun
J
Atsumi
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Kai
K
Obayashi
Division of Bio-System Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University Osaka, Japan.
Shushi
S
Nagamori
Division of Bio-System Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University Osaka, Japan.
Yoshikatsu
Y
Kanai
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Tetsunari
T
Oyama
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine Maebashi, Gunma, Japan.
Izumi
I
Takeyoshi
ASCT2; LAT1; Lung adenocarcinoma; coexpression; prognostic factor; wild-type EGFR