High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas

J Clin Pathol. 2012 Nov;65(11):1019-23. doi: 10.1136/jclinpath-2012-200826. Epub 2012 Jul 19.

Abstract

Background and aims: Molecular target therapy against L-type amino acid transporter 1 (LAT1) is unique and expected to be developed soon. LAT1 expression was investigated in pancreatic cancer as a prognostic predictor.

Methods: Surgically resected pancreatic ductal adenocarcinomas (PDAC, n=66) were investigated using immunohistochemistry. For reference, intraductal papillary mucinous carcinomas (IPMC, including intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia or with an associated invasive carcinoma, n=13) and adenomas (IPMA, including IPMN with low- and intermediate-grade dysplasia, n=5) were also examined.

Results: LAT1 expression scores increased from PDAC to IPMA to IPMC. Kaplan-Meier analysis showed significant differences between LAT1-high and -low scores in PDAC. Even in each Ki-67-labelling index (LI) low and high PDAC group (cut off 40%), high LAT1 expression could also predict poor prognosis. Multivariable analysis showed that LAT1 expression, Ki-67 LI, tumour differentiation and size were individual prognostic factors.

Conclusions: LAT1 aberrant overexpression in PDAC predicts poor prognosis, independent of Ki-67 LI, and offers a potential target for future anticancer therapy with its inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / diagnosis*
  • Adenoma / metabolism
  • Adenoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / diagnosis*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Papillary / diagnosis*
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / mortality
  • Female
  • Humans
  • Japan / epidemiology
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Male
  • Middle Aged
  • Neoplasms, Multiple Primary / diagnosis
  • Pancreatectomy
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Large Neutral Amino Acid-Transporter 1