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Increased expression of senescence‐associated cell cycle regulators in the progression of biliary atresia: an immunohistochemical study
Author(s) -
Sasaki Motoko,
Kuo FangYing,
Huang ChaoCheng,
Swanson Paul E,
Chen ChaoLong,
Chuang JiinHaur,
Yeh Matthew M
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13476
Subject(s) - biliary atresia , senescence , bile duct , cholestasis , immunohistochemistry , biology , atresia , biliary tract , medicine , bile acid , pathology , gastroenterology , cancer research , transplantation , liver transplantation
Aims Cellular senescence plays a role in tumour suppression and in the pathogenesis of various non‐neoplastic diseases, including primary biliary cholangitis and other adult cholangiopathies. Less is known about the role of cellular senescence in cholangiopathies in children. With that in mind, we examined the expression of senescence‐associated cell cycle regulators in biliary atresia, the most common form of paediatric obliterative cholangiopathy. Methods and results The expression of senescence‐associated cell cycle regulators (p16 Ink4a and p21 WAF 1/Cip1 ) and a ductular reaction related marker (neural cell adhesion molecule: NCAM ) was examined in bile ducts and bile ductules in liver samples taken from the patients with biliary atresia [ n = 80; including 23 samples at the time of the Kasai procedure ( KP ) and 63 obtained from the explanted liver ( LT ) (six cases with samples at both surgical stages of disease)] and from appropriate controls ( n = 17). The degree of ductular reaction and cholestasis was significantly more extensive in LT than KP ( P < 0.01). The expression of p16 INK 4a and NCAM was significantly more extensive in bile ducts and bile ductules in ductular reaction in both KP and LT compared to controls and in LT compared to KP ( P < 0.05). The expression of p21 WAF 1/Cip1 was significantly more extensive in bile ducts and bile ductules in KP compared to both LT and controls ( P < 0.01). Conclusions Cellular senescence may play a role in the progression of bile duct loss in biliary atresia in a manner similar to that of adult cholangiopathies.