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- Title
The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study.
- Authors
Gormley, J A; Hegarty, S M; O'Grady, A; Stevenson, M R; Burden, R E; Barrett, H L; Scott, C J; Johnston, J A; Wilson, R H; Kay, E W; Johnston, P G; Olwill, S A
- Abstract
<bold>Background: </bold>The aim of this pilot retrospective study was to investigate the immunohistochemical expression of Cathepsin S (CatS) in three cohorts of colorectal cancer (CRC) patients (n=560).<bold>Methods: </bold>Prevalence and association with histopathological variables were assessed across all cohorts. Association with clinical outcomes was investigated in the Northern Ireland Adjuvant Chemotherapy Trial cohort (n=211), where stage II/III CRC patients were randomised between surgery-alone or surgery with adjuvant fluorouracil/folinic acid (FU/FA) treatment.<bold>Results: </bold>Greater than 95% of tumours had detectable CatS expression with significantly increased staining in tumours compared with matched normal colon (P>0.001). Increasing CatS was associated with reduced recurrence-free survival (RFS; P=0.03) among patients treated with surgery alone. Adjuvant FU/FA significantly improved RFS (hazard ratio (HR), 0.33; 95% CI, 0.12-0.89) and overall survival (OS; HR, 0.25; 95% CI, 0.08-0.81) among 36 patients with high CatS. Treatment did not benefit the 66 patients with low CatS, with a RFS HR of 1.34 (95% CI, 0.60-3.19) and OS HR of 1.33 (95% CI, 0.56-3.15). Interaction between CatS and treatment status was significant for RFS (P=0.02) and OS (P=0.04) in a multivariate model adjusted for known prognostic markers.<bold>Conclusion: </bold>These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC.
- Subjects
NORTHERN Ireland; PROGNOSIS; DIAGNOSTIC use of tumor markers; ADJUVANT treatment of cancer; RETROSPECTIVE studies; COHORT analysis; DIAGNOSTIC immunohistochemistry; COLON cancer patients
- Publication
British Journal of Cancer, 2011, Vol 105, Issue 10, p1487
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2011.408