title: Overexpression of protein S100A4 is independently associated with overall survival in stage C colonic cancer but only in cytoplasm at the advancing tumour front.
abstract: OBJECTIVE
  S100A4, a multifunctional protein, has been linked to the invasive growth and metastases of several human cancers. This study investigated the association between S100A4 and overall survival and other clinicopathological features in patients with stage C colonic cancer.
  
  
  METHODS
  Clinical and pathological data were obtained from a prospective hospital registry of 409 patients who had a resection for stage C colonic cancer. Tissue microarrays for immunohistochemistry were constructed from archived tissue. S100A4 staining intensity and percentage of stained cells were assessed in nuclei and cytoplasm for both the central part of the tumour and at the advancing front. Overall survival was analysed by the Kaplan-Meier method and Cox regression.
  
  
  RESULTS
  Only a high percentage of cells with S100A4 cytoplasmic staining in frontal tissue was associated with poor survival (hazard ratio, 1.6; 95 % CI 1.1-2.2; p = 0.008) after adjustment for other prognostic variables. There was no association between frontal cytoplasmic S100A4 expression and any of 13 other clinicopathological variables.
  
  
  CONCLUSIONS
  High expression of S100A4 in cytoplasm at the advancing front of stage C colonic tumours indicates a poor prognosis. Whether S100A4 can predict response to adjuvant chemotherapy remains to be investigated in a randomised clinical trial.
authors.affiliation: Department of Medicine, Concord Hospital, Sydney, New South Wales, Australia.
authors.forename: P S S
authors.initials: PS
authors.lastname: Kho
authors.forename: L
authors.initials: L
authors.lastname: Jankova
authors.forename: C L-S
authors.initials: CL
authors.lastname: Fung
authors.forename: C
authors.initials: C
authors.lastname: Chan
authors.forename: C
authors.initials: C
authors.lastname: Clarke
authors.forename: B P C
authors.initials: BP
authors.lastname: Lin
authors.forename: G
authors.initials: G
authors.lastname: Robertson
authors.forename: M
authors.initials: M
authors.lastname: Molloy
authors.forename: P H
authors.initials: PH
authors.lastname: Chapuis
authors.forename: E L
authors.initials: EL
authors.lastname: Bokey
authors.forename: O F
authors.initials: OF
authors.lastname: Dent
authors.forename: S
authors.initials: S
authors.lastname: Clarke
mesh_terms: D000328:Adult; D000368:Aged; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012044:Regression Analysis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D013194:Staining and Labeling; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human