Deleted in colon cancer protein expression in colorectal cancer metastases: a major predictor of survival in patients with unresectable metastatic disease receiving palliative fluorouracil-based chemotherapy.
OBJECTIVE
To determine whether deleted in colon cancer (DCC) protein expression in colorectal cancer (CRC) metastases could predict outcome to palliative fluorouracil (FU)-based chemotherapy and to assess whether it is similar to that observed in the corresponding primary tumors.


METHODS
DCC protein expression was assessed immunohistochemically on archival specimens of CRC metastases from 42 patients homogeneously treated by methotrexate-modulated bolus FU alternated to 6-S-leucovorin-modulated infused FU and was retrospectively correlated with patient characteristics and clinical outcome. In a subset analysis, DCC immunoreactivity was compared between metastatic CRC and the corresponding primary tumors and regional lymph node metastases.


RESULTS
Positive immunoreactivity for DCC was found in 45% of patients. Eighteen (78%) of 23 patients for whom multiple samples were available displayed a similar pattern of expression in distant metastases and primary tumors. The median survival time was 14.3 months in patients without DCC expression and 21.4 months in patients with DCC-positive tumors (log-rank test, P =.04); the 2-year survival rates were 8.5% and 42.5%, respectively. Response rates to chemotherapy were not significantly different between the two groups. By multivariate analysis, DCC protein expression maintained its prognostic value and showed to be the single best predictor of survival, with a relative risk of 2.16.


CONCLUSIONS
Our results indicate that expression of the DCC protein in CRC metastases is similar to that observed in the corresponding primary tumors and represents a dominant predictor of survival in patients with unresectable, advanced CRC who are undergoing palliative FU-based chemotherapy.
Aschele
Carlo
C
Department of Medical Oncology, E.O. Ospedali Galliera, Genova, Italy. carlo.aschele@galliera.it
Debernardis
Domizia
D
Lonardi
Sara
S
Bandelloni
Roberto
R
Casazza
Stefania
S
Monfardini
Silvio
S
Gallo
Luigi
L
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000075389:DCC Receptor; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D010166:Palliative Care; D011237:Predictive Value of Tests; D011379:Prognosis; D011956:Receptors, Cell Surface; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate