Article
P53 pathway parameter expression in brain metastases
Expression der P53-Pathway-Parameter in Hirnmetastasen
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Published: | April 23, 2004 |
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Outline
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Objective
Brain metastases are a major and increasingly common complication in cancer treatment. P53-dependent cell cycle control, though not fully understood, is a potential therapeutic target in cancer. The aim of this study was to estimate the expression of p53 pathway parameters p53, MDM2, p21, Bcl-2 and Bax in a large series of brain metastasis.
Methods
Paraffin-embedded tissue specimens from 139 patients were included who had undergone craniotomy for newly diagnosed brain metastases between 05/1994 and 10/2001 at our department. Tumor origin was non-small cell lung cancer (NSCLC; n=78), breast cancer (n=35), colorectal adenocarcinoma (n=17) and renal cancer (n=9). Immunohistochemical staining for p53, MDM2, p21, Bcl-2 and Bax was compared to corresponding primary tumors, to Ki67 proliferation index and patient survival.
Results
In comparison to primary tumors, Bax was significantly over expressed in brain metastases of all tumor types examined (p<0.001). Variable expression differences were noticed for other parameters: p53 expression was decreased in colorectal cancer brain lesions (p=0.048) and lost in renal cancer brain metastases. P21 was overexpressed in NSCLC (p=0.0001), colorectal (p=0.005) and renal cancer brain metastases. Bcl-2 was significantly decreased in breast and colorectal brain metastases (p<0.001) while there was a trend in NSCLC and renal cancer brain lesions. A high Ki67 was significantly associated with reduced survival (p=0.032) whereas there was no correlation between p53, MDM2, p21, Bcl-2 and Bax expression versus survival.
Conclusions
Pro-apoptotic Bax and G1-cell cycle inhibitor p21 were significantly overexpressed in brain metastases of different origin when compared to corresponding primary tumors. In contrast, p53 and anti-apoptotic Bcl-2 expression was decreased. A high Ki67 PI indicated reduced survival while there was no correlation between p53 parameter expression and patient survival.