Gallbladder cancer - gene expression profiling

• Expression of p21^Wafl/Cip1, p57^Kip2 and HER2/neu in Patients with Gallbladder Cancer

Anticancer Research May 1, 2007 vol. 27 no. 3B

H. PUHALLA, F. WRBA, D KANDIOLER,, M. LEHNERT, A. HUYNH, T. GRUENBERGER, D. TAMANDL, and M. FILIPITS

Abstract

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.

Patients And 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).

Conclusion:
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.

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