title: Microsatellite instability and loss of heterozygosity at chromosomal location 18q: prospective evaluation of biomarkers for stages II and III colon cancer--a study of CALGB 9581 and 89803.
abstract: OBJECTIVE
  Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors.
  
  
  METHODS
  We studied two of these genomic defects-mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH)-in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH.
  
  
  RESULTS
  Compared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS.
  
  
  CONCLUSIONS
  We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.
authors: Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. mbertagnolli@partners.org
authors: Monica M
authors: MM
authors: Bertagnolli
authors: Mark
authors: M
authors: Redston
authors: Carolyn C
authors: CC
authors: Compton
authors: Donna
authors: D
authors: Niedzwiecki
authors: Robert J
authors: RJ
authors: Mayer
authors: Richard M
authors: RM
authors: Goldberg
authors: Thomas A
authors: TA
authors: Colacchio
authors: Leonard B
authors: LB
authors: Saltz
authors: Robert S
authors: RS
authors: Warren
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D053842:Microsatellite Instability; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C400149:Edrecolomab