Deleted in colorectal cancer protein expression as a possible predictor of response to adjuvant chemotherapy in colorectal cancer patients

Rivka Gal*, Evgeny Sadikov, Jaqueline Sulkes, Baruch Klein, Rumelia Koren

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1216-1224
Number of pages9
JournalDiseases of the Colon and Rectum
Volume47
Issue number7
DOIs
StatePublished - Jul 2004

Funding

FundersFunder number
Medical Research Fund of the Rabin Medical Center

    Keywords

    • Chemotherapy
    • Chromosome 18q
    • Colorectal cancer
    • Prognosis

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