Deleted in colorectal cancer protein expression as a possible predictor of response to adjuvant chemotherapy in colorectal cancer patients.
OBJECTIVE
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.
Gal
Rivka
R
Department of Pathology, Hasharon Hospital, Petah Tikva, Israel. rumelia@isdnmail.co.il
Sadikov
Evgeny
E
Sulkes
Jaqueline
J
Klein
Baruch
B
Koren
Rumelia
R
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000075389:DCC Receptor; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007978:Levamisole / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D007978:Levamisole; D005472:Fluorouracil