Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in patients with ovarian tumors.
OBJECTIVE
Amino acid transporters are essential for the growth, progression and the pathogenesis of various cancers. However, it remains obscure about the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and system ASC amino acid transporter 2 (ASCT2) for patients with human ovarian tumors. The aim of this study is to elucidate the prognostic role of these amino acid transporters in ovarian tumor.


METHODS
One-hundred forty-two patients with surgically resected ovarian tumors were analyzed by immunohistochemistry. Expression of LAT1, ASCT2, CD98, Ki-67 and microvessel density (MVD) determined by CD34 were evaluated using specimens of the resected tumors.


RESULTS
LAT1 and ASCT2 were positively expressed in 39% and 53%, respectively, of ovarian tumors (n=142) and 50% and 57%, respectively, of epidermal ovarian cancers (n=107). A positive LAT1 expression was closely correlated with the expression for ASCT2 and CD98, and cell proliferation (Ki-67) in ovarian cancer. By multivariate analysis, LAT1 was clarified as a significant independent marker for predicting a poor overall survival (OS). The expression of LAT1 could clearly discriminate between epidermal ovarian cancer and borderline malignancy. The expression level of LAT1 within ovarian cancer cells varied among serous adenocarcinoma, endometrioid adenocarcinoma, clear cell adenocarcinoma and mucinous adenocarcinoma and we found LAT1 expression was higher in clear cell adenocarcinoma than other histological types.


CONCLUSIONS
LAT1 is highly expressed in various ovarian tumors and a positive LAT1 expression can serve as a significant independent factor for predicting a poor OS in patients with epidermal ovarian cancer.
Department of Oncology Clinical Development, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan ; Department of Oncology Center, Gunma University Hospital Showa-machi, Maebashi, Gunma, Japan.
Kyoichi
K
Kaira
Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan ; Department of Gynecology, Gunma Prefectural Cancer Center Oota, Gunma, Japan.
Kazuto
K
Nakamura
Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan.
Takashi
T
Hirakawa
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan.
Hisao
H
Imai
Advanced Clinical Research Center, Fukushima Medical University Fukushima, Japan.
Hideyuki
H
Tominaga
Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan.
Noboru
N
Oriuchi
Division of Bio-system Pharmacology, Graduate School of Medicine, Osaka University Osaka, Japan.
Shushi
S
Nagamori
Division of Bio-system Pharmacology, Graduate School of Medicine, Osaka University Osaka, Japan.
Yoshikatsu
Y
Kanai
Department of Oncology Center, Gunma University Hospital Showa-machi, Maebashi, Gunma, Japan.
Norifumi
N
Tsukamoto
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan.
Tetsunari
T
Oyama
Department of Oncology Clinical Development, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan.
Takayuki
T
Asao
Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan.
Takashi
T
Minegishi
ASCT2; LAT1; amino acid transporter; ovarian cancer; prognosis