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

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.

Keywords: Non-small-cell lung carcinoma, LAT1, mRNA, Protein, RT-PCR, Immunohistochemistry, Prognosis