Fascin overexpression is involved in carcinogenesis and prognosis of human intrahepatic cholangiocarcinoma: immunohistochemical and molecular analysis.
Fascin is an actin-bundling protein that induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been associated with progression or prognosis in various neoplasms; however, its role in intrahepatic cholangiocarcinoma is unknown. Tumor sections from 84 patients with intrahepatic cholangiocarcinoma and 16 patients with intrahepatic biliary dysplasia were stained with antifascin antibody. Fascin mRNA expression, measured by real-time reverse transcription-polymerase chain reaction in 20 frozen samples, was compared with the immunohistochemical results. Furthermore, the expression of cyclin D1 was compared with that of fascin. Immunohistochemically, fascin expression was absent or sporadic in normal biliary epithelium, whereas high expression (>70% of tumor cells) was found in 2 (12.5%) dysplasias and 30 (35.7%) intrahepatic cholangiocarcinomas. The difference between the fascin mRNA concentrations in the high-expression and low-expression groups was significant (P = .0082). Tumors showing high expression were poorly differentiated (P = .0019), and among poorly differentiated intrahepatic cholangiocarcinoma, larger tumors (>5 cm) were more likely than smaller lesions to have high fascin expression (P = .0205). A significant correlation was observed between fascin and cyclin D1 immunoreactivity (P = .0289). Patients whose tumors expressed fascin abundantly had a poorer outcome (P = .0085), and fascin overexpression was an independent prognostic factor (P = .0477). Fascin is expressed early in biliary carcinogenesis and might contribute to poor differentiation and to growth of intrahepatic cholangiocarcinoma. It is a significant indicator of a poor prognosis for patients with intrahepatic cholangiocarcinoma.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Tomohiro
T
Iguchi
Shinichi
S
Aishima
Akinobu
A
Taketomi
Yunosuke
Y
Nishihara
Nobuhiro
N
Fujita
Kensaku
K
Sanefuji
Keishi
K
Sugimachi
Yo-ichi
Y
Yamashita
Yoshihiko
Y
Maehara
Masazumi
M
Tsuneyoshi
D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C020324:fascin