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Volume 68, Issue 1, Pages 58-65 (April 2010)


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LAT1 expression in non-small-cell lung carcinomas: Analyses by semiquantitative reverse transcription-PCR (237 cases) and immunohistochemistry (295 cases)

Katsuyuki Takeuchia, Sho Ogatab, Kuniaki NakanishibCorresponding Author Informationemail address, Yuichi Ozekic, Sadayuki Hiroib, Susumu Tominagab, Shinsuke Aidad, Hirotaka Matsuoe, Tsuneaki Sakataf, Toshiaki Kawaib

Received 12 December 2008; received in revised form 26 March 2009; accepted 28 May 2009. published online 26 June 2009.

Abstract 

Objective

System l-amino acid transport mediates the uptake of aromatic neutral amino acids and nutritionally essential amino acids from extracellular fluids. Little is known about the role of l-amino acid transporter 1 (LAT1), a member of the system l-amino acid transporter family, in non-small-cell lung carcinomas (NSCLCs).

Patients and methods

We examined (i) LAT1 mRNA levels in 40 normal lung tissues (NLTs) and 237 NSCLCs using semiquantitative RT-PCR, (ii) LAT1 protein expression in 295 NSCLCs using immunohistochemistry, and (iii) whether LAT1 mRNA and protein expressions were related to clinicopathologic findings and outcome.

Results

The LAT1 mRNA level was significantly higher in all NSCLCs (6.81±1.13) than in NLT (1.00±0.18). The LAT1 mRNA level showed no association with clinicopathologic findings or outcome. LAT1 protein was detected with a diffuse or granular appearance within the cytoplasm and/or on the plasma membrane of tumor cells. When tumors were graded as positive if staining indicating a plasma membrane expression of LAT1 protein made up more than 10% of the tumor, the frequency of this membrane expression was found to be associated with tumor histology, differentiation grade, pathologic stage, T classification, pleural invasion, lymph-vessel invasion, and overall survival rate.

Conclusion

Detection of a plasma membrane expression of LAT1 protein would appear to be of value in informing the prognosis in NSCLC cases.

a Division of Molecular Pharmacology, Department of Biosystems Science, Graduate School of Science and Technology, Kobe University, Nada 657-8601, Japan

b Department of Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan

c Department of Surgery, National Defense Medical College, Tokorozawa 359-8513, Japan

d Department of Laboratory Medicine, National Defense Medical College Hospital, Tokorozawa 359-8513, Japan

e Department of Physiology, National Defense Medical College, Tokorozawa 359-8513, Japan

f Division of Molecular Pharmacology, Department of Biology, Graduate School of Science, Kobe University, Nada 657-8601, Japan

Corresponding Author InformationCorresponding author at: Department of Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan. Tel.: +81 42 995 1505; fax: +81 42 996 5192.

PII: S0169-5002(09)00322-5

doi:10.1016/j.lungcan.2009.05.020


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