Immunoprofiles of 11 biomarkers using tissue microarrays identify prognostic subgroups in colorectal cancer.
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.
Knösel
Thomas
T
Institute of Pathology, Charité-Campus Mitte, Berlin, Germany.
Emde
Anna
A
Schlüns
Karsten
K
Chen
Yuan
Y
Jürchott
Karsten
K
Krause
Matthias
M
Dietel
Manfred
M
Petersen
Iver
I
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
D014408:Biomarkers, Tumor; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26