Source:http://linkedlifedata.com/resource/pubmed/id/10398083
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1999-8-23
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pubmed:abstractText |
Defects in the mechanisms controlling the cell cycle are crucial in cell transformation and/or tumour progression. p21WAF1/CIP1 is an inhibitor of cyclin-dependent kinases, induced by p53-dependent and p53-independent pathways, which can block progression through the cell cycle. p21WAF1/CIP1 expression has been investigated immunohistochemically in a series of 191 patients with colorectal cancer of known p53 status. The purpose of the study was two-fold: to assess the relationship between p21WAF1/CIP1 immunoreactivity and p53 alterations, and to evaluate the prognostic significance of p21WAF1/CIP1 expression. In 96 carcinomas (51 per cent), p21WAF1/CIP1 was expressed in over 10 per cent of tumour cells, whereas in 26, p21WAF1/CIP1 was detected in under 10 per cent of neoplastic cells; 69 tumours lacked p21WAF1/CIP1 expression. Immunoreactivity was more frequent in tumours of the right colon (p < 0.003) and was inversely correlated with tumour stage (p < 0.03), p53 gene mutations (p < 0.0007), p53 protein accumulation (p < 0.019), and Bcl-2 expression (p < 0.0005). In univariate analysis, down-regulation of p21WAF1/CIP1 expression was associated with poor overall (p = 0.0022) and disease-free survival (p = 0.0009). Multivariate analysis, however, did not confirm any independent prognostic significance of p21WAF1/CIP1 expression. The results indicate that p21WAF1/CIP1 is associated with abnormal accumulation of p53 protein and the occurrence of p53 gene mutations in colorectal cancer and that lack of p21WAF1/CIP1 expression is correlated with reduced patient survival in univariate analysis. These data underline the crucial pathogenetic role of the p53-p21WAF1/CIP1 pathway in carcinomas of the large bowel.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-3417
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
187
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
302-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10398083-Adenocarcinoma,
pubmed-meshheading:10398083-Colorectal Neoplasms,
pubmed-meshheading:10398083-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:10398083-Cyclins,
pubmed-meshheading:10398083-Female,
pubmed-meshheading:10398083-Follow-Up Studies,
pubmed-meshheading:10398083-Genes, p53,
pubmed-meshheading:10398083-Humans,
pubmed-meshheading:10398083-Immunoenzyme Techniques,
pubmed-meshheading:10398083-Intestinal Mucosa,
pubmed-meshheading:10398083-Male,
pubmed-meshheading:10398083-Mutation,
pubmed-meshheading:10398083-Neoplasm Proteins,
pubmed-meshheading:10398083-Neoplasm Staging,
pubmed-meshheading:10398083-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10398083-Survival Rate,
pubmed-meshheading:10398083-Tumor Markers, Biological
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pubmed:year |
1999
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pubmed:articleTitle |
p21WAF1/CIP1 expression in colorectal carcinoma correlates with advanced disease stage and p53 mutations.
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pubmed:affiliation |
Department of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan School of Medicine, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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