Disruption of pRb-p16INK4 pathway: a common event in ampullary carcinogenesis.
OBJECTIVE
Aberrations of the pRb (Retinoblastoma gene protein)-p16INK4 pathway play a critical role in carcinogenesis. Our objective is to evaluate its role in tumorigenesis and the development of ampullary cancer.


METHODS
We examined expression status of p16INK4 protein and pRb immunohistochemically and assessed their possible prognostic relevance in 36 ampullary cancers.


RESULTS
Thirty-four specimens (94.4%) exhibited alteration of p16INK4 and/or pRb expression, with 63.9% (23/36) of cancers showing p16INK4 negative expression and 94.4% (34/36) pRb abnormal expression. p16INK4 protein negative expression correlated significantly with tumor progression features such as advanced tumor stages (p=0.0291), lymph node metastasis (p=0.005), pancreas invasion (p=0.0002) and duodenum invasion (p=0.0101). Cases with both p16RNK4 protein negative expression and pRb overexpression showed poorer differentiation, more invasive growth (p=0.0425), higher level tumor stages (p=0.0079) and more frequent pancreas invasion (p=0.0024), compared with the others. p16INK4 protein expression showed no relationship with pRb expression (p=0.2199). No association was found in pRb expression status compared with any clinicopathological parameters analyzed.


CONCLUSIONS
The disruption of the pRb-p16NK4 pathway plays an important role in ampullary carcinogenesis, the absence of p16INK4 protein expression might be involved in ampullary tumor progression.
Yuan
Lian-Wen
LW
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine University of Tokyo, Tokyo, Japan.
Tang
Wei
W
Kokudo
Norihiro
N
Seyama
Yasujgi
Y
Shi
Ya-Zhou
YZ
Karako
Hirona
H
Zhao
Bin
B
Sugawara
Yasuhiko
Y
Nagawa
Hirokazu
H
Makuuchi
Masatoshi
M
D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000378:metabolism* / Q000473:pathology; D003138:Common Bile Duct Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012189:Retrospective Studies
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein