title: Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer.
abstract: OBJECTIVE
  The prognostic value of the degree of apoptosis in colorectal cancer is controversial. This study evaluates the putative clinical usefulness of measuring caspase-3 activity as a prognostic factor in colonic cancer patients receiving 5-fluoracil adjuvant chemotherapy.
  
  
  METHODS
  We evaluated caspase-3-like protease activity in tumours and in normal colon tissue. Specimens were studied from 54 patients. These patients had either stage III cancer (Dukes stage C) or high-risk stage II cancer (Dukes stage B2 with invasion of adjacent organs, lymphatic or vascular infiltration or carcinoembryonic antigen [CEA] >5). Median follow-up was 73 months. Univariate analysis was performed previously to explore the relation of different variables (age, sex, preoperative CEA, tumour size, Dukes stage, vascular invasion, lymphatic invasion, caspase-3 activity in tumour and caspase-3 activity in normal mucosa) as prognostic factors of tumour recurrence after chemotherapy treatment. Subsequently, a multivariate Cox regression model was performed.
  
  
  RESULTS
  Median values of caspase-3 activity in tumours were more than twice those in normal mucosa (88.1 vs 40.6 U, p=0.001), showing a statistically significant correlation (r=0.34). Significant prognostic factors of recurrence in multivariate analysis were: male sex (odds ratio, OR=3.53 [1.13-10.90], p=0.02), age (OR=1.09 [1.01-1.18], p=0.03), Dukes stage (OR=1.93 [1.01-3.70]), caspase-3 activity in normal mucosa (OR=1.02 [1.01-1.04], p=0.017) and caspase-3 activity in tumour (OR=1.02 [1.01-1.03], p=0.013).
  
  
  CONCLUSIONS
  Low caspase-3 activity in the normal mucosa and tumour are independent prognostic factors of tumour recurrence in patients receiving adjuvant 5-fluoracil-based treatment in colon cancer, correlating with poor disease-free survival and higher recurrence rate.
authors.affiliation: Departament of Surgery, Hospital Universitario de Bellvitge, Feixa Llarga s/n, 08907 LHospitalet de Llobregat, Barcelona, Spain. jdeoca@ub.edu
authors.forename: Javier
authors.initials: J
authors.lastname: de Oca
authors.forename: Daniel
authors.initials: D
authors.lastname: Azuara
authors.forename: Raquel
authors.initials: R
authors.lastname: Sanchez-Santos
authors.forename: Matilde
authors.initials: M
authors.lastname: Navarro
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Anna
authors.initials: A
authors.lastname: Sola
authors.forename: Georgina
authors.initials: G
authors.lastname: Hotter
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Biondo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Osorio
authors.forename: Joan
authors.initials: J
authors.lastname: Martí-Ragué
authors.forename: Antoni
authors.initials: A
authors.lastname: Rafecas
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome