Frequent expression of mucin core protein MUC1 in non‐neoplastic gallbladder mucosa from patients with pancreaticobiliary maljunction

Yamato, Taro; Kuroda, Hiroshi; Ohama, Kazunori; Yamamichi, Noboru; Watanabe, Y; Harada, Kenichi; Sasaki, Motoko; Nakanuma, Yasuni

doi:10.1111/j.1478-3231.1999.tb00050.x

Cited by 15 publications

(17 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[1][2][3] PBM is defined as the union of the pancreatic and common bile ducts outside the wall of the duodenum, beyond the influence of the sphincter of Oddi. [3][4][5][6][7] Normally, the pancreaticobiliary duct and junction are governed by sphincter, but as a result of the anomaly, pancreatic juice can reflex into the common bile duct. PBM patients are known to be associated with bile duct dilatation and also biliary tract carcinoma, especially in the Far East.…”

mentioning

confidence: 99%

“…PBM patients are known to be associated with bile duct dilatation and also biliary tract carcinoma, especially in the Far East. [3][4][5][6][7] Patients who develop gallbladder carcinoma in association with PBM are usually 10 years younger than those without PBM. Synchronous primary cancers of the gallbladder and common bile duct have also been associated with PBM.…”

mentioning

confidence: 99%

“…[3][4][5] It has been postulated in PBM that the reflex of pancreatic juice into the common bile duct and the stagnation of pancreatic juice mixed with bile have been considered to play an important role in the pathophysiology of PBM, including biliary tract carcinoma. [3][4][5][6][7][8][9][10] A high concentration of lysolecithin (LL) was reported in the gallbladder bile of PBM, [3][4][5][6][7] and LL is produced from lecithin by activated phospholipase A2 in the refluxing pancreatic juice in PBM. LL and other altered bile components may be responsible for the development of PHP and also carcinoma of the gallbladder in PBM.…”

mentioning

confidence: 99%

“…LL and other altered bile components may be responsible for the development of PHP and also carcinoma of the gallbladder in PBM. [3][4][5][6][7] Although gallstones seem to be closely associated with gallbladder carcinoma, there is no evidence of direct causal relationship between them. Lining epithelia of the biliary tract including the gallbladder are known to show intraepithelial atypical/proliferative lesions closely associated with the development of carcinoma.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Papillary hyperplasia of the gallbladder in pancreaticobiliary maljunction represents a senescence-related lesion induced by lysolecithin

Yamaguchi

Sasaki

Harada

et al. 2009

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

Cellular senescence, an irreversible growth arrest, is considered to play as safeguard against malignant progression, though such a mechanism is speculative in human carcinogenesis. In gallbladder carcinoma, cholecystolithiasis and pancreaticobiliary maljunction (PBM) are major risk factors. Here, by using 113 surgically resected gallbladders and cultures of human gallbladder epithelial cells (HGECs) and gallbladder carcinoma cell line (TGBC2TKB), we examined carcinogenesis with respect to cellular senescence. Among 15 cases of PBM in which carcinoma was found in 4 cases, nonneoplastic gallbladder mucosa showed diffuse papillary hyperplasia (PHP). PHP was not found in gallbladders with cholecystolithiasis. Interestingly, PHP exhibited senescent features such as expression of p16INK4A and low cell proliferative activity. In contrast, EZH2, a polycomb group protein, was overexpressed in intraepithelial neoplasm and carcinoma in gallbladders with cholecystolithiasis. In PBM, EZH2 was expressed only in carcinoma foci but not in PHP. Cultured HGECs treated with lysolecithin, the level of which is elevated in gallbladder bile of PBM, showed increased expression of p16INK4A and senescence-associated b-galactosidase. Conversely, enforced overexpression of EZH2 in senescent HGECs reduced p16 INK4A expression. A knockdown of EZH2 in cultured TGBC2TKB cells increased p16 INK4aexpression. In conclusion, PHP in PBM may act as a barrier to malignant transformation for decades. EZH2 may be responsible for the escape from cellular senescence followed by malignant transformation in the gallbladder of PBM.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Papillary hyperplasia of the gallbladder in pancreaticobiliary maljunction represents a senescence-related lesion induced by lysolecithin

Yamaguchi

Sasaki

Harada

et al. 2009

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

show abstract

“…In consideration of these facts, a hyperplasia-dysplasia-carcinoma sequence can be suggested in the carcinogenesis process in PBM [25,26]. Overexpression of cyclooxygenase-2 and vascular endothelial growth factor [27] and mucin core protein [28] were reported in the hyperplastic biliary epithelia of PBM patients.…”

Section: Pathological Findingsmentioning

confidence: 98%

Biliary carcinogenesis in pancreaticobiliary maljunction

et al. 2016

View full text Add to dashboard Cite

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Because of the excessive length of the common channel in PBM, sphincter action does not directly affect the pancreaticobiliary junction, which allows pancreatic juice to reflux into the biliary tract. According to the results of a nationwide survey, bile duct and gallbladder cancers were found in 6.9 and 13.4 % of adult patients with congenital biliary dilatation, respectively, and in 3.1 and 37.4 % of those with PBM without biliary dilatation, respectively. Biliary tract cancers develop about 15-20 years earlier in patients with PBM than in individuals without PBM; they sometimes develop as double cancers. Carcinogenesis is strongly associated with stasis of bile intermingled with refluxed pancreatic juice. Epithelial cells in the biliary tract of PBM patients are under constant attack from activated pancreatic enzymes, increased secondary bile acids, or other mutagens. This can result in hyperplastic change with increased cell proliferation activity, and in turn, oncogene and/or tumor suppressor gene mutations in the epithelia, leading to the biliary tract carcinogenesis. The carcinogenesis of biliary tract cancer accompanying PBM is considered to involve a hyperplasia-dysplasia-carcinoma sequence induced by chronic inflammation caused by the reflux of pancreatic juice into the biliary tract, which differs from the adenoma-carcinoma sequence or the de novo carcinogenesis associated with biliary tract cancers in the population without PBM. Patients with a relatively long common channel have a similar, albeit slightly lower, risk for gallbladder cancer compared with PBM patients.

show abstract

Elevated bile amylase level without pancreaticobiliary maljunction is a risk factor for gallbladder carcinoma

Fujimoto

Ohtsuka

Nakashima

et al. 2017

J Hepato Biliary Pancreat

View full text Add to dashboard Cite

show abstract

Frequent expression of mucin core protein MUC1 in non‐neoplastic gallbladder mucosa from patients with pancreaticobiliary maljunction

Cited by 15 publications

References 19 publications

Papillary hyperplasia of the gallbladder in pancreaticobiliary maljunction represents a senescence-related lesion induced by lysolecithin

Papillary hyperplasia of the gallbladder in pancreaticobiliary maljunction represents a senescence-related lesion induced by lysolecithin

Biliary carcinogenesis in pancreaticobiliary maljunction

Elevated bile amylase level without pancreaticobiliary maljunction is a risk factor for gallbladder carcinoma

Contact Info

Product

Resources

About