title: Immunoprofiles of 11 biomarkers using tissue microarrays identify prognostic subgroups in colorectal cancer.
abstract: OBJECTIVE
  Genomewide expression profiling has identified a number of genes expressed at higher levels in colorectal cancer (CRC) than in normal tissues. Our objectives in this study were: 1) to test whether genes were also distinct on the protein level; 2) to evaluate these biomarkers in a series of well-characterized CRCs; and 3) to apply hierarchical cluster analysis to the immunohistochemical data.
  
  
  METHODS
  Tissue microarrays (TMAs) comprising 351 CRC specimens from 270 patients were constructed to evaluate the genes Adam10, Cyclin D1, Annexin II, NFKB, Casein kinase 2 beta (CK2B), YB-1, P32, Rad51, c-fos, IGFBP4, and Connexin26 (Cx26). In total, 3,797 samples were analyzed.
  
  
  RESULTS
  Unsupervised hierarchical clustering discovered subgroups of CRC that differed by tumor stage and survival. Kaplan-Meier analysis showed that reduced Cx26 expression was significantly associated with shorter patient survival and higher tumor grade (G1/G2 vs G3, P = .02), and Adam10 expression with a higher tumor stage (pT1/2 vs pT3/4, P = .04).
  
  
  CONCLUSIONS
  Our study highlights the potential of TMAs for a higher-dimensional analysis by evaluating serial sections of the same tissue core (three-dimensional TMA analysis). In addition, it endorses the use of immunohistochemistry supplemented by hierarchical clustering for the identification of tumor subgroups with diagnostic and prognostic signatures.
authors.affiliation: Institute of Pathology, Charité-Campus Mitte, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Knösel
authors.forename: Anna
authors.initials: A
authors.lastname: Emde
authors.forename: Karsten
authors.initials: K
authors.lastname: Schlüns
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Karsten
authors.initials: K
authors.lastname: Jürchott
authors.forename: Matthias
authors.initials: M
authors.lastname: Krause
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000072259:Connexin 26; D017630:Connexins; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26