High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas.
OBJECTIVE
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.
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. czp05616@nifty.com
Nobuyuki
N
Yanagisawa
Masaaki
M
Ichinoe
Tetuo
T
Mikami
Norihiro
N
Nakada
Kiyomi
K
Hana
Wasaburo
W
Koizumi
Hitoshi
H
Endou
Isao
I
Okayasu
D000236:Adenoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D027283:Large Neutral Amino Acid-Transporter 1