Expression of p21(Wafl/Cip1), p57(Kip2) and HER2/neu in patients with gallbladder cancer.
BACKGROUND
To improve the prognosis of gallbladder cancer (GC) patients, a better understanding of the mechanisms of tumor development and progression is essential. The deregulation of cell cycle control is a critical step in the development of cancer. The purpose of this study was to investigate the expression of p21(Wafl/Cip1), p57(Kip2) and HER2/neu in an unselected GC patient population and to assess the association of these markers with p27(Kip1) expression, p53 gene mutation status and clinical parameters of the patients.


METHODS
Formalin-fixed paraffin-embedded tissues from 55 operated GC patients were used to determine the expression of p21(Wafl/Cip1), p57(Kip2) and HER2/neu with immunohistochemistry.


RESULTS
Expression of p21(Wafl/Cip1) was observed in 28%, of p57(Kip2) in 19% and of HER2/neu in 13% of the patients. Absence of p57(Kip2) expression was significantly associated with T3/T4 stage (p = 0.01), positive lymph nodes (p = 0.02) and advanced UICC stages (p = 0.05). HER2/neu expression significantly correlated with advanced T stages (p = 0.02). In the total patient population, p21(Wafl/Cip1), p57(Kip2) and HER2/neu had no impact on survival of the patients. Among patients with a mutated p53 gene, those without p21(Wafl/Cip1) expression had a prolonged survival compared to patients with p21(Wafl/Cip1) expression (p = 0.004). Moreover, in p27(Kip1)-positive patients, those without p21(Wafl/Cip1) expression had a longer survival than those with p21(Wafl/Cip1) expression (p = 0.003).


CONCLUSIONS
In the subgroup of patients with a mutated p53 gene or in p27(Kip1)-positive patients, absence of p21(Wafl/Cip1) expression may be associated with longer survival of GC patients. Therefore, further analyses of this protein in larger patient populations are warranted.
Puhalla
H
H
Department of Surgery, Division of General Surgery, Medical University of Vienna, Vienna, Austria.
Wrba
F
F
Kandioler
D
D
Lehnert
M
M
Huynh
A
A
Gruenberger
T
T
Tamandl
D
D
Filipits
M
M
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis* / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000032:analysis* / Q000378:metabolism; D005260:Female; D005706:Gallbladder Neoplasms / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016612:Paraffin Embedding; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism; D013534:Survival; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human