The DCC Protein and Prognosis in Colorectal Cancer
David Shibata, M.D., Michael A. Reale, M.D., Ph.D., Philip Lavin, Ph.D., Mark Silverman, M.D., Eric R. Fearon, M.D., Ph.D., Glenn Steele, M.D., Ph.D., John M. Jessup, M.D., Massimo Loda, M.D., and Ian C. Summerhayes, Ph.D.
Background Allelic loss of chromosome 18q predicts a poor outcomein patients with stage II colorectal cancer. Although the specificgene 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 intumor cells is a prognostic marker in colorectal carcinoma.
Methods The expression of DCC was evaluated immunohistochemicallyin 132 paraffin-embedded samples from patients with curativelyresected stage II or III colorectal carcinomas. The Cox proportional-hazardsmodel was used to adjust for covariates including age, sex,tumor site, degree of tumor differentiation, and use of adjuvanttherapy.
Results The expression of DCC was a strong positive predictivefactor for survival in both stage II and stage III colorectalcarcinomas. In patients with stage II disease whose tumors expressedDCC, the five-year survival rate was 94.3 percent, whereas inpatients with DCC-negative tumors, the survival rate was 61.6percent (P<0.001). In patients with stage III disease, therespective survival rates were 59.3 percent and 33.2 percent(P = 0.03).
Conclusions DCC is a prognostic marker in patients with stageII or stage III colorectal cancer. In stage II colorectal carcinomas,the absence of DCC identifies a subgroup of patients with lesionsthat behave like stage III cancers. These findings may thushave therapeutic implications in this group of patients.
Source Information
From the Laboratory of Cancer Biology, Department of Surgery (D.S., G.S., J.M.J., I.C.S.), and the Department of Pathology (M.L.), New England Deaconess Hospital, Harvard Medical School, Boston; the Section of Medical Oncology, Yale University School of Medicine, New Haven, Conn. (M.A.R.); the Boston Biostatistics Research Foundation, Framingham, Mass. (P.L.); the Department of Pathology, Lahey–Hitchcock Medical Center, Burlington, Mass. (M.S.); and the Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor (E.R.F.).
Address reprint requests to Dr. Summerhayes at the Laboratory of Cancer Biology, SWRL 3, Department of Surgery, New England Deaconess Hospital, 1 Deaconess Rd., Boston, MA 02215.
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