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

Lung Cancer. 2010 Apr;68(1):58-65. doi: 10.1016/j.lungcan.2009.05.020. Epub 2009 Jun 25.

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry*
  • Large Neutral Amino Acid-Transporter 1 / genetics
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction*

Substances

  • Large Neutral Amino Acid-Transporter 1