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. 2014 Apr 15;110(8):2030-9.
doi: 10.1038/bjc.2014.88. Epub 2014 Mar 6.

ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer

K Shimizu  1 , K Kaira  2 , Y Tomizawa  3 , N Sunaga  4 , O Kawashima  5 , N Oriuchi  6 , H Tominaga  7 , S Nagamori  8 , Y Kanai  8 , M Yamada  4 , T Oyama  9 , I Takeyoshi  1
Affiliations

ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer

K Shimizu et al. Br J Cancer. .

Abstract

Background: ASC amino-acid transporter 2 (ASCT2) is a major glutamine transporter that has an essential role in tumour growth and progression. Although ASCT2 is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear.

Methods: One hundred and four patients with surgically resected NSCLC were evaluated as one institutional cohort. Tumour sections were stained by immunohistochemistry (IHC) for ASCT2, Ki-67, phospho-mTOR (mammalian target of rapamycin), and CD34 to assess the microvessel density. Two hundred and four patients with NSCLC were also validated by IHC from an independent cohort.

Results: ASC amino-acid transporter 2 was expressed in 66% of patients, and was closely correlated with disease stage, lymphatic permeation, vascular invasion, CD98, cell proliferation, angiogenesis, and mTOR phosphorylation, particularly in patients with adenocarcinoma (AC). Moreover, two independent cohorts confirmed that ASCT2 was an independent marker for poor outcome in AC patients.

Conclusions: ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery.

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Figures

Figure 1
Figure 1
Immunohistochemical staining of tumour tissue from a 68-year-old male with a pulmonary SQC (A) and a 70-year-old female with a pulmonary AC (B). ASCT2 exhibited a membranous immunostaining pattern (A, score of 4; B, score of 3).
Figure 2
Figure 2
Kaplan–Meier analysis of OS correlated with ASCT2 expression in the NGH and GUH cohorts. A statistically significant difference in OS was observed between the patients with positive and negative tumour expression of ASCT2 in all patients in the NGH (A) and GUH (D) cohorts. When OS was separated by histology, a statistically significant difference was identified in patients with AC in the NGH (B) and GUH (E) cohorts, but not in those with non-AC in NGH (C) and GUH (F).
See this image and copyright information in PMC

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