High expression of L-type amino-acid transporter 1 (LAT1) in gastric carcinomas: comparison with non-cancerous lesions

Pathol Int. 2011 May;61(5):281-9. doi: 10.1111/j.1440-1827.2011.02650.x. Epub 2011 Mar 17.

Abstract

Amino acid transporters are essential for maintenance and proliferation of both normal and transformed cells. In the present study, L-type amino-acid transporter 1 (LAT1) immunoreactive expression was investigated in gastric carcinomas, in comparison with gastric adenomas and non-neoplastic lesions, using our recently developed novel monoclonal antibody. In a total of 87 cases of advanced gastric cancer, high LAT1 expression was observed in carcinoma cells, predominantly at plasma membranes with greater intensity in non-scirrhous than scirrhous carcinomas. Gastric carcinoma cases with lymph node metastasis showed significantly higher LAT1 expression than cases without lymph node metastasis. A positive correlation with Ki-67 LI was observed and the highly expressing non-scirrhous carcinomas showed a significantly poorer prognosis than the low LAT1 group. Cox hazard test revealed that TNM stage and LAT1 expression were independent prognostic factors in non-scirrhous carcinoma group. Further, a significant poor prognosis was confirmed in high LAT1 expression group, when limited to undifferentiated carcinoma cases excluding scirrhous carcinoma. Lower levels were found in adenomas. In conclusion, LAT 1 expression may be linked with cell proliferation and prognosis of gastric carcinomas, and offers a potential target for future anticancer therapy by inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenoma / metabolism*
  • Adenoma / mortality
  • Adenoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Female
  • Gastric Mucosa / metabolism
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / immunology
  • Ki-67 Antigen / metabolism
  • Large Neutral Amino Acid-Transporter 1 / immunology
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / mortality
  • Precancerous Conditions / pathology
  • Prognosis
  • Proportional Hazards Models
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Protein p53 / immunology
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Large Neutral Amino Acid-Transporter 1
  • Tumor Suppressor Protein p53