title: Prognostic significance of calcium-binding protein S100A4 in colorectal cancer.
abstract: OBJECTIVE
  Prognostication in colon cancer almost exclusively still rests on the tumor stage. Furthermore, tumor-derived markers to improve discrimination of low- and high-risk subtypes generally are not in use. S100A4 has been reported to be associated with invasion and metastasis; however, no data are available on its prognostic value in colorectal carcinoma. Therefore, we investigated the prognostic significance of immunohistochemical S100A4 expression in colorectal carcinoma compared with clinicopathologic parameters and expression of cell-cycle markers p16, p21, p27, p53, Ki-67, and RB.
  
  
  METHODS
  Archival tissue from 709 patients with colorectal cancer were retrieved, applied in tissue array technology, and investigated immunohistochemically. Univariate and multivariate survival analyses were carried out on all investigated parameters.
  
  
  RESULTS
  Sixteen percent of cases showed high; 31%, low; and 53%, no S100A4 expression. In Kaplan-Meier analysis, S100A4 positively stained cases showed a significantly decreased survival time compared with negatively stained cases (P < 0.0001). In multivariate regression analysis, S100A4 expression emerged as a highly significant independent parameter (P < 0.001) with the highest relative-risk factor among other covariates. Nodal status (pN) lost its prognostic value if S100A4 was added to the model. High S100A4 expression was associated with tumor stage pT3/4, secondary metastasis, women, p16, and RB expression.
  
  
  CONCLUSIONS
  S100A4 expression represents a highly significant prognostic marker in colorectal carcinoma, which is able to identify a subset of patients at high risk. In this respect, it is superior to established prognostic markers such as nodal status, pT stage, and p53 expression.
authors.affiliation: Department of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gongoll
authors.forename: Gerrit
authors.initials: G
authors.lastname: Peters
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Pompiliu
authors.initials: P
authors.lastname: Piso
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klempnauer
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Reinhard
authors.initials: R
authors.lastname: von Wasielewski
mesh_terms: D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human