The DCC protein and prognosis in colorectal cancer.
BACKGROUND
Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma.


METHODS
The expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II and III colorectal carcinomas. The Cox proportional-hazards model was used to adjust for covariates including age, sex, tumor site, degree of tumor differentiation, and use of adjuvant therapy.


RESULTS
The expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the five-year survival rate was 94.3 percent, whereas in patients with DCC-negative tumors, the survival rate was 61.6 percent (P<0.001). In patients with stage III disease, the respective survival rates were 59.3 percent and 33.2 percent (P=0.03).


CONCLUSIONS
DCC is a prognostic marker in patients with stage II or stage III colorectal cancer. In stage II colorectal carcinomas, the absence of DCC identifies a subgroup of patients with lesions that behave like stage III cancers. These findings may thus have therapeutic implications in this group of patients.
Shibata
D
D
Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215, USA.
Reale
M A
MA
Lavin
P
P
Silverman
M
M
Fearon
E R
ER
Steele
G
G
Jessup
J M
JM
Loda
M
M
Summerhayes
I C
IC
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000075389:DCC Receptor; D005260:Female; D015870:Gene Expression; D016163:Genes, DCC / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface; D015996:Survival Rate; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins