title: A simple immunohistochemical algorithm predicts the risk of distant metastases in right-sided colon cancer.
abstract: OBJECTIVE
  A test predicting distant metastases would be valuable for prognostication in colon cancer (CC). In previous studies, CC with microsatellite instability (MSI) showed a reduced risk of distant metastases. High expression of CD133 and β-catenin, both related to cancer stem cell phenotypes, might be predictive markers for metastasis. The aim of this study was to develop a simple and robust test for risk assessment of distant metastases in CC.
  
  
  RESULTS
  In a case-control study, 57 cases of right-sided CC specimens with synchronous distant metastases were matched with 57 CC without distant metastases. Immunohistochemistry for MLH1, CD133 and nuclear β-catenin was carried out. To define the diagnostic algorithm the tumours were first stratified according to their MLH1 expression. Loss of MLH1 expression was correlated significantly with a very low risk of distant metastases (5.3%; P = 0.00003). In MLH1-positive cases, combined high scores of CD133 and β-catenin were associated with a very high rate of distant metastases (94.4%), whereas the risk was intermediate for carcinomas with either low CD133 and/or low β-catenin expression (P = 0.0007). A validation study using an independent set of 68 right-sided CC specimens showed a clear trend towards risk stratification according to the algorithm; however, sample sizes were small, and associations were not statistically significant.
  
  
  CONCLUSIONS
  By the use of three markers, this algorithm allowed identification of subgroups of right-sided CC patients with extremely high and extremely low risk of distant metastases.
authors.affiliation: Pathologisches Institut der Ludwig-Maximilians-Universität München, Germany. jens.neumann@med.uni-muenchen.de
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.forename: David
authors.initials: D
authors.lastname: Horst
authors.forename: Lydia
authors.initials: L
authors.lastname: Kriegl
authors.forename: Susanne
authors.initials: S
authors.lastname: Maatz
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
mesh_terms: D000071916:AC133 Antigen; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000368:Aged; D000465:Algorithms; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D018570:Risk Assessment; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D006023:Glycoproteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1