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Prognostic Value of p27, p53, and Vascular Endothelial Growth Factor in Dukes A and B Colon Cancer Patients Undergoing Potentially Curative Surgery

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Diseases of the Colon & Rectum

PURPOSE

Early-stage colon cancer patients (Dukes A or B; pT1–T3 pNO pMO) are excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, 20 percent to 30 percent of these patients ultimately succumb from recurrent disease. This indicates that the conventional staging procedures may be unable to precisely predict cancer prognosis.

METHODS

In 65 early-stage colon cancers, we investigated by immunohistochemistry the role of molecular markers such as p27, p53, and vascular endothelial growth factor in identifying high-risk patients who may benefit from adjuvant treatments.

RESULTS

No clinicopathologic factor, namely Dukes stage, t parameter, number of resected nodes, and vascular or lymphatic invasion, was found be an independent significant predictor of disease-specific and disease-free survival. In contrast, each molecular marker predicted survival and recurrence rates much better than the conventional Dukes staging system. The best combination of variables for prediction of long-term outcome and recurrence rate included p27, p53, and vascular endothelial growth factor. Interestingly, the greater the number of molecular alterations, the lower the five-year estimated survival function. Nearly all cancer-related deaths were observed among patients whose colon cancers expressed all three molecular alterations. Regardless of Dukes stage, the recurrence rate was found to increase with the increase in the number of molecular alterations. Early-stage colon cancers expressing p27 down-regulation and high p53 and vascular endothelial growth factor immunoreactivity showed a 100 percent actuarial four-year recurrence rate.

CONCLUSIONS

Assessment of molecular alterations may be useful to identify a higher-risk group of early-stage colon cancer patients who may benefit from adjuvant chemotherapy.

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ACKNOWLEDGMENT

The authors thank Dr. Bert Vogelstein (Johns Hopkins Medical Institutions, Baltimore, Maryland) for helpful discussions and invaluable collaboration.

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Authors and Affiliations

  1. Division of Surgical Oncology, “F. Magrassi–A. Lanzara” Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy

    Gennaro Galizia M.D., Ph.D., Eva Lieto M.D., Paolo Castellano M.D., Ph.D., Vincenzo Imperatore M.D., Mario Vollaro M.D., Ph.D. & Carlo Pignatelli M.D., Ph.D.

  2. Division of Pathology, “F. Magrassi–A. Lanzara” Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy

    Francesca Ferraraccio M.D. & Bruno Agostini M.D., Ph.D.

  3. Division of Medical Oncology, “F. Magrassi–A. Lanzara” Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy

    Michele Orditura M.D., Ph.D. & Ferdinando De Vita M.D., Ph.D.

  4. Division of Clinical Immunology, “F. Magrassi–A. Lanzara” Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy

    Ciro Romano M.D., Ph.D.

Authors
  1. Gennaro Galizia M.D., Ph.D.
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  2. Francesca Ferraraccio M.D.
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  3. Eva Lieto M.D.
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  4. Michele Orditura M.D., Ph.D.
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  5. Paolo Castellano M.D., Ph.D.
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  6. Vincenzo Imperatore M.D.
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  7. Ciro Romano M.D., Ph.D.
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  8. Mario Vollaro M.D., Ph.D.
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  9. Bruno Agostini M.D., Ph.D.
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  10. Carlo Pignatelli M.D., Ph.D.
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  11. Ferdinando De Vita M.D., Ph.D.
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Correspondence to Gennaro Galizia M.D., Ph.D..

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Galizia, G., Ferraraccio, F., Lieto, E. et al. Prognostic Value of p27, p53, and Vascular Endothelial Growth Factor in Dukes A and B Colon Cancer Patients Undergoing Potentially Curative Surgery. Dis Colon Rectum 47, 1904–1914 (2004). https://doi.org/10.1007/s10350-004-0695-8

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  • DOI: https://doi.org/10.1007/s10350-004-0695-8

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