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. 2014 May 13;110(10):2506-13.
doi: 10.1038/bjc.2014.178. Epub 2014 Apr 24.

Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer

M Toyoda  1 , K Kaira  2 , Y Ohshima  3 , N S Ishioka  3 , M Shino  1 , K Sakakura  1 , Y Takayasu  1 , K Takahashi  1 , H Tominaga  4 , N Oriuchi  5 , S Nagamori  6 , Y Kanai  6 , T Oyama  7 , K Chikamatsu  1
Affiliations

Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer

M Toyoda et al. Br J Cancer. .

Abstract

Background: Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer.

Methods: Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53.

Results: L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis.

Conclusions: L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.

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Figures

Figure 1
Figure 1
Representative immunohistochemical staining of patient with tongue squamous cell carcinoma. Immunostaining of LAT1 (A), ASCT2 (B), and xCT (C) displays a membranous immunostaining pattern.
Figure 2
Figure 2
Kaplan–Meier analysis of overall survival (OS) and progression-free survival (PFS) according to LAT1, ASCT2, and xCT expression. A statistically significant difference in OS and PFS was observed between the patients with high LAT1 and those with low LAT1 tumour expression (OS, P<0.001(A); PFS, P=0.009 (B)), and between the patients with positive and negative ASCT2 tumour expression (OS, P=0.012 (C); PFS, P=0.033 (D)). No statistically significant difference in OS (E) and PFS (F) was observed between the patients with positive xCT and those with negative xCT tumour expression.
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