title: Cost analysis of biomarker testing for mismatch repair deficiency in node-positive colorectal cancer.
abstract: BACKGROUND
  Microsatellite instability (MSI) in colorectal cancer is caused by defective DNA mismatch repair (MMR). It is present in 15 per cent of sporadic colorectal cancers owing to epigenetic mutL homologue 1 (MLH1) inactivation. The evidence suggests that patients with tumours caused by defective DNA MMR do not benefit from 5-fluorouracil (5-FU)-based chemotherapy.
  
  
  METHODS
  The proportion of cancers with defective DNA MMR identified by MSI analysis or immunohistochemistry was calculated from published data. The cost of analysis was compared with the potential savings if 5-FU-based chemotherapy was not administered to these patients.
  
  
  RESULTS
  Some 16.3 per cent of sporadic colorectal cancers had defective DNA MMR. Immunostaining for MLH1 and mutS homologue 2 (MSH2) had a sensitivity of 92.4 per cent and a specificity of 99.6 per cent for identifying MSI-high tumours. The strongest predictive variable was right-sidedness, with positive and negative predictive values of 0.329 and 0.948 respectively. If 5-FU-based chemotherapy were not administered, potential savings of up to pound 1.2 million per 1000 patients tested could be made. Costs would be higher if alternative chemotherapeutic regimens were substituted as a result of testing.
  
  
  CONCLUSIONS
  Knowledge of MMR status may enable participation in trials of non-5-FU-based chemotherapy. The cost of MMR testing may be offset by more efficient use of chemotherapy.
authors.affiliation: Department of General Surgery, Manchester Royal Infirmary, St Mary's Hospital, Manchester, UK. emma.barrow@doctors.org.uk
authors.forename: E
authors.initials: E
authors.lastname: Barrow
authors.forename: R
authors.initials: R
authors.lastname: McMahon
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.forename: E
authors.initials: E
authors.lastname: Levine
authors.forename: J
authors.initials: J
authors.lastname: Hill
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000191:economics / Q000235:genetics; D017046:Cost Savings; D003362:Cost-Benefit Analysis; D053843:DNA Mismatch Repair; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics; D008207:Lymphatic Metastasis; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009687:Nuclear Proteins; D011237:Predictive Value of Tests
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein