p53 genetic alterations, protein expression and autoantibodies in human colorectal carcinoma: A comparative study

Rana Hallak, Joerg Mueller, Oliver Lotter, Susanne Gansauge, Frank Gansauge, Muhi El Deen Jumma, Mathias Montenarh, Farouk Safi, Hans Beger

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

This study investigated a total number of 120 colorectal malignant tumor tissues by applying a new quantitative luminometric assay (LIA)-mat, immunohistochemistry (IHC) (n=100), PCR/SSCP (n=42), and sequencing (n=7). Sera were collected from 235 patients suffering from colorectal carcinoma in addition to 195 healthy individuals as a control group. Manual ELISA kit was developed to detect p53 autoantibodies in the sera of those patients. Our data demonstrated that the LIA-mat yields reliable estimates of p53 expression in soluble cell extracts as compared with results obtained by immunohistochemistry which showed positive immunostaining in 63% of the studied cases. Using a cut-off value of 1.8 ng/mg protein, 65 tumors out of 120 (54%) were classified to be positive by LIA-mat, manifesting protein overexpression, while 22 out of 42 (52%) tumor samples showed p53 gene alteration when applying single strand conformation polymorphism (SSCP) analysis on polymerase chain reaction products. In tumor samples without a p53 gene alteration, the median soluble p53 protein level was 4.3 ng/mg protein, whereas the median p53 protein level for tumor samples with p53 gene alteration was 7.5 times higher. Despite a significant correlation between the outcome of LIA and SSCP, a disagreement was found in 30% of cases. We found no significant correlation between p53 protein overexpression and clinicopathological findings except for distant metastasis (p=0.33), indicating p53 immunoreactivity to be an independent prognostic factor. Our data showed that 18% of patients suffering from colorectal cancer developed autoantibodies against p53 in their sera which might be an early indicator for tumor development and distant metastasis.

Original languageEnglish
Pages (from-to)785-791
Number of pages7
JournalInternational journal of oncology
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 1998
Externally publishedYes

Keywords

  • Colorectal carcinoma
  • Quantitative luminometric assay
  • p53 autoantibodies
  • p53 gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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