Tumorigenesis and phenotypic characteristics of mucin-producing bile duct tumors: an immunohistochemical approach.
Intraductal papillary neoplasm of the bile duct (IPNB) is characterized by exophytic proliferation of neoplastic epithelial cells with fibrovascular stalks in bile duct lumen, mucin hypersecretion, and considerable dilatation or multilocular changes of the affected bile ducts. A mucin-producing bile duct tumor is an IPNB with excessive mucin production and clinical symptoms. Herein, the phenotypes as well as the tumorigenesis and progression of IPNB are reviewed with immunohistochemical assistance. The tumors are subdivided into three phenotypes: pancreatobiliary, intestinal, and gastric. About half of IPNB cases are of the pancreatobiliary type, and the remaining half are of the intestinal type. Aberrant expression of CDX2 with MUC2 and CK20 is related to the development of intestinal metaplasia. Inactivation of P16INK4a and nuclear expression of beta-catenin are related to the development of IPNB. Decreased expression of membranous beta-catenin and E-cadherin and aberrant expression of MMP-7 and -9 and of MUC1 are related to invasion of IPNB with tubular adenocarcinoma, whereas MUC2 is involved in the invasion of IPNB with mucinous carcinoma. IPNB can be regarded as a counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, particularly the main duct type. More comparative studies between IPNB and pancreatic IPMN are recommended for further analysis of these papillary neoplasms.
Nakanuma
Yasuni
Y
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-8640, Japan. pbcpsc@kenroku.kanazawa-u.ac.jp
Zen
Yoh
Y
Harada
Kenichi
K
Ikeda
Hiroko
H
Sato
Yasunori
Y
Uehara
Takeshi
T
Sasaki
Motoko
M
D002288:Adenocarcinoma, Mucinous / Q000473:pathology; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071616:CDX2 Transcription Factor; D015820:Cadherins / Q000378:metabolism; D044584:Carcinoma, Ductal / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism*; D018281:Cholangiocarcinoma; D019938:Cyclin D1 / Q000378:metabolism; D018450:Disease Progression; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018396:Mucin-1 / Q000378:metabolism; D055262:Mucin-2 / Q000378:metabolism; D009077:Mucins / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology; D010641:Phenotype; D051176:beta Catenin / Q000378:metabolism
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D053554:Keratin-20; C060192:MUC1 protein, human; C524625:MUC2 protein, human; D018396:Mucin-1; D055262:Mucin-2; D009077:Mucins; D051176:beta Catenin; D019938:Cyclin D1; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9