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Deleted in Colorectal Cancer Protein Expression as a Possible Predictor of Response to Adjuvant Chemotherapy in Colorectal Cancer Patients

  • Original Contribution
  • Published:
Diseases of the Colon & Rectum

PURPOSE:

The deleted in colorectal cancer (DCC) gene predicts a poor outcome for patients with colorectal carcinoma. This study was designed to investigate whether the expression of the DCC protein also can predict response to adjuvant chemotherapy.

METHODS:

The expression of DCC was evaluated immunohistochemically in 74 paraffin-embedded tumor samples from patients with Stage II (n = 41) and Stage III (n = 33) colorectal carcinomas. Follow-up time was at least 60 (median, 64) months. Follow-up was at least five years for all patients who are alive. End points of the study were recurrence of disease and death. Forty-eight patients received adjuvant therapy of 5-fluorouracil + levamisole; 28 were not treated.

RESULTS:

Fifty percent of tumors were deleted in colorectal cancer-positive (DCC+). Proportion of survival and disease-free survival were higher in the DCC+ patients (83 percent) than in deleted in colorectal cancer-negative (DCC−; 54 percent). In the DCC+ group, adjuvant treatment was a strong positive predictive factor for survival and disease-free survival. All DCC+ patients who received adjuvant chemotherapy (CHEMO+) are alive with no evidence of disease, whereas without chemotherapy (CHEMO−) only 54 percent are alive (P = 0.0001). When stratification was performed by stage, patients in Stage II who were DCC+/CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO− survival rate was 75 percent and disease-free survival rate 62 percent (P = 0.042). Patients in Stage III who were DCC+/ CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO− both dropped to zero (P = 0.0002). On the other hand, in the DCC− tumors, there was no statistical significant relationship between chemotherapy and survival or disease-free survival (DCC−/CHEMO− had 57 percent survival; DCC−/CHEMO+ had 52 percent survival).

CONCLUSIONS:

DCC is a prognostic factor for colorectal cancer. Positive expression of DCC identifies a subgroup of patients who respond favorably to adjuvant chemotherapy, which resulted in our cases, in 100 percent survival and disease-free survival rates. Without treatment, the survival rate of DCC+ patients dropped significantly. We suggest that DCC immunostaining should be performed routinely. All DCC+ patients should receive adjuvant chemotherapy. For DCC− tumors, a larger cohort of patients should be studied before definitive conclusions can be drawn; however, clinical trials of new drug combinations should focus on DCC− patients.

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ACKNOWLEDGMENTS

The authors thank Hannah Gertzman for the excellent technical assistance, and Miriam Kleiner and Yossi Sadovnic for photographs.

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Authors and Affiliations

  1. Department of Pathology, Hasharon Hospital, Petah Tikva, Israel

    Rivka Gal M.D. & Rumelia Koren M.D.

  2. Department of Oncology, Hasharon Hospital, Petah Tikva, Israel

    Evgeny Sadikov M.D. & Baruch Klein M.D.

  3. Epidemiology Unit, Rabin Medical Center, Petah Tikva, Israel

    Jaqueline Sulkes Ph.D.

  4. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Rivka Gal M.D., Jaqueline Sulkes Ph.D., Baruch Klein M.D. & Rumelia Koren M.D.

Authors
  1. Rivka Gal M.D.
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  2. Evgeny Sadikov M.D.
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  3. Jaqueline Sulkes Ph.D.
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  4. Baruch Klein M.D.
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  5. Rumelia Koren M.D.
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Correspondence to Rivka Gal M.D..

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Reprints are not available.

Supported in part by a grant from the Medical Research Fund of the Rabin Medical Center.

Presented in part at the 4th World Congress on Advances in Oncology and 2nd International Symposium on Molecular Medicine, Vouliagmeni, Athens, Greece, October 7 to 9, 1999.

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Gal, R., Sadikov, E., Sulkes, J. et al. Deleted in Colorectal Cancer Protein Expression as a Possible Predictor of Response to Adjuvant Chemotherapy in Colorectal Cancer Patients. Dis Colon Rectum 47, 1216–1224 (2004). https://doi.org/10.1007/s10350-004-0552-9

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  • DOI: https://doi.org/10.1007/s10350-004-0552-9

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