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

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International Journal of Colorectal Disease Aims and scope Submit manuscript

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.

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Acknowledgements

We thank Drs. Kornelia Polyak and Roger Greenberg (Harvard Medical School) for helpful suggestions during the preparation of the manuscript and Blaženka Ladika (University Hospital Sestre milosrdnice) for excellent assistance with the p53-Ab in vitro studies. This work was supported by the grant 134002 from the Croatian Ministry of Science and Technology (to J.L.).

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Authors and Affiliations

  1. Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA, 02115, USA

    Mirna Lechpammer, Stanislav Lechpammer & Massimo Loda

  2. Department of Oncology and Nuclear Medicine, University Hospital Sestre milosrdnice, Vinogradska c. 29, 10000, Zagreb, Croatia

    Josip Lukač & Zvonko Kusić

  3. Department of Surgery, University Hospital Sestre milosrdnice, Vinogradska c. 29, 10000, Zagreb, Croatia

    Dujo Kovačević

  4. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Massimo Loda

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  1. Mirna Lechpammer
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  2. Josip Lukač
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  3. Stanislav Lechpammer
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  4. Dujo Kovačević
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  5. Massimo Loda
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  6. Zvonko Kusić
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Correspondence to Mirna Lechpammer.

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Lechpammer, M., Lukač, J., Lechpammer, S. et al. Humoral immune response to p53 correlates with clinical course in colorectal cancer patients during adjuvant chemotherapy. Int J Colorectal Dis 19, 114–120 (2004). https://doi.org/10.1007/s00384-003-0553-5

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  • DOI: https://doi.org/10.1007/s00384-003-0553-5

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