Humoral immune response to p53 correlates with clinical course in colorectal cancer patients during adjuvant chemotherapy

Int J Colorectal Dis. 2004 Mar;19(2):114-20. doi: 10.1007/s00384-003-0553-5. Epub 2003 Nov 21.

Abstract

Background and aims: Overexpression of p53 protein in malignancies induces an immune response in some cancer patients. We investigated whether production of serum antibodies against p53 (p53-Ab) is associated with pathohistological parameters of colorectal carcinoma and whether p53-Ab can serve as a tumor marker during cancer treatment.

Patients and methods: Serum samples from 220 colorectal cancer patients during surgery and adjuvant chemotherapy and 42 healthy controls were tested for the presence of p53-Ab by ELISA. Expression of p53 protein in tumors was determined using mouse anti-human p53-Ab.

Results: Serum p53-Ab were detected in 18% of patients while all controls were negative. A strong correlation between p53-Ab production and p53 protein expression was observed: 70% of p53-Ab positive cases had tumors positive for p53 vs. 52% of p53-Ab negative cases. There was also a significant predominance of p53-Ab positive cases in Dukes' stages B and C over stage A. Although surgery alone reduced p53-Ab levels, decreases in p53-Ab titer became significant midterm through chemotherapy compared to both pre- and postoperative values and remained decreased until the completion of treatment.

Conclusion: The presence of p53-Ab in sera of patients with colorectal cancer indicates tumors in more advanced histopathologic stages (Dukes' B, C). Due to low sensitivity (18%) p53-Ab are not recommendable as a preoperative marker for colorectal cancer. However, due to high specificity (100%), their monitoring after surgery and adjuvant chemotherapy has potential for early diagnosis of tumor relapse in p53-Ab positive cases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neoplasm / blood*
  • Antibody Formation
  • Autoantibodies / blood*
  • Biomarkers, Tumor / immunology*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Tumor Suppressor Protein p53 / immunology*

Substances

  • Antibodies, Neoplasm
  • Autoantibodies
  • Biomarkers, Tumor
  • Tumor Suppressor Protein p53