TY - JOUR
T1 - Human REG I gene is up-regulated in intrahepatic cholangiocarcinoma and its precursor lesions
AU - Harada, Kenichi
AU - Zen, Yoh
AU - Kanemori, Yoshiko
AU - Chen, Tse Ching
AU - Chen, Miin Fu
AU - Yeh, Ta Sen
AU - Jan, Yi Yin
AU - Masuda, Shinji
AU - Nimura, Yuji
AU - Takasawa, Shin
AU - Okamoto, Hiroshi
AU - Nakanuma, Yasuni
N1 - Funding Information:
Supported by research grants for “hepatolithiasis” from the Japanese Health and Welfare Ministry (Chairman: Prof. Yuji Nimura, Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan) and also for “intrahepatic cholangiocarcinoma” from the Japanese Education Ministry (Chairman: Prof. Yuji Nimura).
PY - 2001
Y1 - 2001
N2 - The Reg I gene (regenerating gene) and its product (Reg protein) are a regenerating and/or proliferating factor(s) of pancreatic islet cells. The ectopic expression of REG Iα was shown in colorectal carcinomas, suggesting that REG Iα is related to their carcinogenesis. In this study, we examined the expression of REG I in intrahepatic cholangiocarcinoma (ICC) and its precursor lesion (biliary dysplasia). By polymerase chain reaction and in situ hybridization (ISH) studies using a total of 16 fresh liver specimens, REG Iα mRNA was demonstrated in 6 of 11 (55%) ICC cases, but in 0 of 5 (0%) normal livers. Immunohistochemistry for REG I protein was performed in 100 formalin-fixed, paraffin-embedded sections obtained from the 18 cases of ICC alone, 45 hepatolithiasis with ICC (n = 19) or biliary dysplasia (n =26), 21 hepatolithiasis alone (all with hyperplasia), and 16 normal livers. In ICC, the expression of REG I protein was significantly dependent on the histologic differentiation; 12 of 13 (92%) cases in papillary and well-differentiated, 6 of 16 (38%) cases in moderately differentiated, and 0 of 8 (0%) cases in poorly differentiated types. Moreover, in the lesions of hyperplasia, low-grade dysplasia, and high-grade dysplasia in hepatolithiasis, REG I protein was expressed in 4 of 21 (19%), 7 of 12 (58%), and 13 of 14 (93%) cases, respectively. In normal liver, intrahepatic bile ducts were constantly negative for REG I protein. These findings suggest that neoexpression of REG I is a good marker for biliary mucosa at risk for development of ICC, and also that REG I plays a role in the early stages of biliary carcinogenesis, probably via a cell-proliferative effect.
AB - The Reg I gene (regenerating gene) and its product (Reg protein) are a regenerating and/or proliferating factor(s) of pancreatic islet cells. The ectopic expression of REG Iα was shown in colorectal carcinomas, suggesting that REG Iα is related to their carcinogenesis. In this study, we examined the expression of REG I in intrahepatic cholangiocarcinoma (ICC) and its precursor lesion (biliary dysplasia). By polymerase chain reaction and in situ hybridization (ISH) studies using a total of 16 fresh liver specimens, REG Iα mRNA was demonstrated in 6 of 11 (55%) ICC cases, but in 0 of 5 (0%) normal livers. Immunohistochemistry for REG I protein was performed in 100 formalin-fixed, paraffin-embedded sections obtained from the 18 cases of ICC alone, 45 hepatolithiasis with ICC (n = 19) or biliary dysplasia (n =26), 21 hepatolithiasis alone (all with hyperplasia), and 16 normal livers. In ICC, the expression of REG I protein was significantly dependent on the histologic differentiation; 12 of 13 (92%) cases in papillary and well-differentiated, 6 of 16 (38%) cases in moderately differentiated, and 0 of 8 (0%) cases in poorly differentiated types. Moreover, in the lesions of hyperplasia, low-grade dysplasia, and high-grade dysplasia in hepatolithiasis, REG I protein was expressed in 4 of 21 (19%), 7 of 12 (58%), and 13 of 14 (93%) cases, respectively. In normal liver, intrahepatic bile ducts were constantly negative for REG I protein. These findings suggest that neoexpression of REG I is a good marker for biliary mucosa at risk for development of ICC, and also that REG I plays a role in the early stages of biliary carcinogenesis, probably via a cell-proliferative effect.
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U2 - 10.1053/jhep.2001.24168
DO - 10.1053/jhep.2001.24168
M3 - Article
C2 - 11343228
AN - SCOPUS:0035038022
VL - 33
SP - 1036
EP - 1042
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 5
ER -