Increased incidence of p53 mutations is associated with hepatic metastasis in colorectal neoplastic progression.

TitleIncreased incidence of p53 mutations is associated with hepatic metastasis in colorectal neoplastic progression.
Publication TypeJournal Article
Year of Publication1995
AuthorsKastrinakis WV, Ramchurren N, Rieger KM, Hess DT, Loda M, Steele G, Summerhayes IC
Date Published1995 Aug 17
KeywordsAmino Acid Sequence, Base Sequence, Cell Line, Codon, Colonic Neoplasms, Colorectal Neoplasms, DNA Primers, Exons, Genes, p53, Humans, Liver Neoplasms, Molecular Sequence Data, Point Mutation, Polymerase Chain Reaction, Precancerous Conditions, Tumor Cells, Cultured

Within a panel of 15 colon carcinoma cell lines we have characterized the p53 gene status using immunocytochemistry (ICC), SSCP and direct sequence analysis. Extension of this analysis to the use of ICC on 104 colonic lesions, representative of different stages of colonic neoplastic progression, showed an absence of detectable p53 nuclear staining in preneoplastic polyp lesions (20 cases) with staining of 52% (25/48) of primary colon carcinomas and 81% (29/36) of hepatic metastases, suggestive of an increased incidence of p53 mutations in late stage lesions of colonic cancer. To address this issue more directly, we analysed 18 primary colon carcinomas and hepatic metastases excised coincidentally from the same patients. In ICC, p53 nuclear staining was recorded in matching lesions from eight individuals where direct sequencing revealed identical mutations in each case. In four individuals no ICC staining was detected in either lesion and molecular analysis revealed wild type sequence in exons 4-9. In six individuals p53 nuclear staining was observed in the hepatic metastases of patients but not the primary lesion. Molecular analysis revealed point mutation events in hepatic metastases from these patients which were not detected in the primary tumor. The point mutations identified in colon carcinomas were predominantly transition events (83%) located in previously characterized colon hotspot regions. These results demonstrate an increased incidence of p53 mutations associated with secondary lesions of colorectal tumors suggestive of a role for p53 in the establishment of colorectal hepatic metastases.

Alternate JournalOncogene
PubMed ID7651727
Grant ListCA42944 / CA / NCI NIH HHS / United States
CA44704 / CA / NCI NIH HHS / United States
T32 CA 09580 / CA / NCI NIH HHS / United States
Related Faculty: 
Massimo Loda, M.D.

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