PMID- 11003620
OWN - NLM
STAT- MEDLINE
DCOM- 20001019
LR  - 20171116
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 32
IP  - 4 Pt 1
DP  - 2000 Oct
TI  - Up-regulation of fas ligand at early stages and down-regulation of Fas at 
      progressed stages of intrahepatic cholangiocarcinoma reflect evasion from immune 
      surveillance.
PG  - 761-9
AB  - We examined immunohistochemically the possible participation of the Fas/Fas 
      ligand (FasL) system in intrahepatic cholangiocarcinoma (ICC) during the escape 
      from immune surveillance, using 68 cases of ICC, 29 cases of normal intrahepatic 
      large bile ducts, and 18 cases of biliary dysplasia. Apoptosis of 
      tumor-infiltrating lymphocytes (TIL) was examined by terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL). Fas was weakly expressed in 
      normal intrahepatic bile ducts. Almost all biliary dysplasia and 
      well-differentiated ICCs showed moderate to marked expression of Fas, while Fas 
      expression was variable in moderately and poorly differentiated ICCs. 
      Down-regulation of Fas expression was significantly correlated with histologic 
      de-differentiation, vascular invasion, the size of ICCs, and short survival of 
      ICC patients. By in situ hybridization, FasL mRNA were frequently and strongly 
      expressed in biliary dysplasia compared with non-neoplastic intrahepatic bile 
      duct. In well-differentiated ICCs, FasL mRNA expression was frequent and intense. 
      But, the expression gradually decreased in moderately and poorly differentiated 
      ICCs. Down-regulation of FasL mRNA expression in ICCs was correlated with 
      perineural invasion and tumor size (over 4 cm) (P <.05). Apoptotic TIL were more 
      frequent in ICC foci than in non-neoplastic foci remote from ICC foci. These 
      findings suggest that a tumor evasion mechanism involving Fas/FasL exists in ICC; 
      frequent and intense expression of FasL mRNA in well-differentiated ICCs enable 
      them to escape immune surveillance by counterattacking Fas-bearing TIL. This 
      counterattack becomes insensitive in poorly differentiated ICCs, in which the 
      down-regulation of Fas gives them a resistance against the FasL-expressing TIL. 
      These mechanisms may be involved in the tumor progression.
FAU - Shimonishi, T
AU  - Shimonishi T
AD  - Department of Pathology (II), Kanazawa University School of Medicine, Kanazawa, 
      Japan.
FAU - Isse, K
AU  - Isse K
FAU - Shibata, F
AU  - Shibata F
FAU - Aburatani, I
AU  - Aburatani I
FAU - Tsuneyama, K
AU  - Tsuneyama K
FAU - Sabit, H
AU  - Sabit H
FAU - Harada, K
AU  - Harada K
FAU - Miyazaki, K
AU  - Miyazaki K
FAU - Nakanuma, Y
AU  - Nakanuma Y
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (fas Receptor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Apoptosis
MH  - Bile Duct Neoplasms/*immunology/mortality/pathology
MH  - Bile Ducts/metabolism
MH  - *Bile Ducts, Intrahepatic
MH  - Cholangiocarcinoma/*immunology/mortality/pathology
MH  - Fas Ligand Protein
MH  - Female
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Membrane Glycoproteins/*biosynthesis/genetics
MH  - Middle Aged
MH  - RNA, Messenger/analysis
MH  - fas Receptor/*physiology
EDAT- 2000/09/26 11:00
MHDA- 2000/10/21 11:01
CRDT- 2000/09/26 11:00
PHST- 2000/09/26 11:00 [pubmed]
PHST- 2000/10/21 11:01 [medline]
PHST- 2000/09/26 11:00 [entrez]
AID - S0270913900942447 [pii]
AID - 10.1053/jhep.2000.18192 [doi]
PST - ppublish
SO  - Hepatology. 2000 Oct;32(4 Pt 1):761-9. doi: 10.1053/jhep.2000.18192.