RT Journal Article
SR Electronic
T1 Cathepsin B Expression and Survival in Colon Cancer: Implications for Molecular Detection of Neoplasia
JF Cancer Epidemiology Biomarkers & Prevention
JO Cancer Epidemiol Biomarkers Prev
FD American Association for Cancer Research
SP cebp.0529.2010
DO 10.1158/1055-9965.EPI-10-0529
A1 Chan, Andrew T
A1 Baba, Yoshifumi
A1 Shima, Kaori
A1 Nosho, Katsuhiko
A1 Chung, Daniel C
A1 Hung, Kenneth E
A1 Mahmood, Umar
A1 Madden, Karen
A1 Poss, Kirtland
A1 Ranieri, Audrey C
A1 Shue, Daniel S
A1 Kucherlapati, Raju S
A1 Fuchs, Charles S
A1 Ogino, Shuji
YR 2010
UL http://cebp.aacrjournals.org/content/early/2010/09/07/1055-9965.EPI-10-0529.abstract
AB Background: Proteases play a critical role in tumorigenesis and are upregulated in colorectal cancer and neoplastic polyps. In animal models, cathepsin B activatable imaging agents demonstrate high enzyme activity within intestinal tumors. Methods: We conducted a prospective cohort study of 558 men and women with colon cancer with tumors that were accessible for immunohistochemical assessment. We used Cox proportional hazards models, stratified by stage, to compute colon cancer-specific and overall mortality according to tumoral expression of cathepsin B. Results: Among 558 participants, 457 (82%) had tumors that expressed cathepsin B (CTSB-positive) and 101 (18%) had tumors that did not express cathepsin B (CTSB-negative). Cathepsin B expression was not associated with disease stage (P=0.19). After a median follow-up of 11.6 years, there were 254 total and 155 colon cancer-specific deaths. Compared with participants with CTSB-negative tumors, participants with CTSB-positive tumors experienced a multivariate hazard ratio for colon cancer-specific mortality of 1.99 (95% CI, 1.19-3.34) and overall mortality of 1.71 (95% CI, 1.16-2.50). Cathepsin B expression was independently associated with KRAS (p=0.01) and BRAF mutation (p=0.04), but not MSI status, CIMP status, PIK3CA mutation, LINE-1 methylation, p53 expression, or COX-2 expression. Among 123 individuals with adenomas, 91% expressed cathepsin B. Conclusions: As assessed by immunohistochemistry, cathepsin B is expressed in the vast majority of colon cancers, independent of stage, and is significantly associated with higher risk of colon cancer-specific and overall mortality. These results support the potential of cathepsin B as a target for image detection of neoplastic lesions in humans.