The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study.

Abstract

BACKGROUND:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSION:

These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC.

• Authors: J A Gormley, S M Hegarty, A O'Grady, M R Stevenson, R E Burden, H L Barrett, C J Scott, J A Johnston, R H Wilson, E W Kay, P G Johnston, S A Olwill
• Journal: British journal of cancer (Br J Cancer) Vol. 105 Issue 10 Pg. 1487-94 (Nov 08 2011) ISSN: 1532-1827 [Electronic] England
• PMID: 21989182 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: 2011 Cancer Research UK

Chemical References

• Biomarkers, Tumor
• Cathepsins
• cathepsin S
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Cathepsins (metabolism)
• Chemotherapy, Adjuvant
• Cohort Studies
• Colorectal Neoplasms (drug therapy, enzymology, surgery)
• Female
• Fluorouracil (administration & dosage)
• Humans
• Immunohistochemistry
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Pilot Projects
• Prognosis