Prognostic role of beta-catenin and p53 expression in the metastatic progression of sporadic colorectal cancer.
Beta-catenin and p53 play key roles in tumorigenesis. The relationships between these 2 signaling pathways and their contribution to colorectal cancer metastatic progression have not been completely elucidated. We analyzed 141 cases of primary sporadic colorectal cancer, 45 matched metastases, and 80 samples of normal mucosa by immunohistochemistry on paraffin-embedded specimens. The expression profiles were also related to patients' clinicopathologic features and 5-year survival. In primary tumors, beta-catenin immunoreactivity was nuclear (27%), predominantly membrane/cytosolic (46.0%) or negative (27%). This latter subgroup was strongly related to microsatellite instability, in particular to MLH-1 deficiency. Remarkably, beta-catenin membrane/cytosolic expression in primary tumors was reduced in the corresponding matched metastases. p53 showed a significant increase in immunoreactivity in (66.7%), whereas it was negative in (33.3%) of tumors. When we considered the expression of both genes, the combination of negative beta-catenin and positive p53 nuclear staining (21%) was strongly related to a higher frequency of liver metastases. Such an association was significantly related to a worse prognosis than any other combination. In a multivariate analysis, beta-catenin and distant metastases were independent prognostic markers. We suggest that a combination of low beta-catenin and high p53 expression in primary colorectal cancers may be a prognostic factor in predicting the progression of the disease, the occurrence of metastasis, and a more severe outcome.
Department of Biological and Environmental Sciences, University of Sannio, 82100 Benevento, Italy.
Massimo
M
Pancione
Nicola
N
Forte
Alessandra
A
Fucci
Lina
L
Sabatino
Antonio
A
Febbraro
Arturo
A
Di Blasi
Bruno
B
Daniele
Domenico
D
Parente
Vittorio
V
Colantuoni
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D051176:beta Catenin / Q000096:biosynthesis*
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D000070957:MutL Protein Homolog 1