title: Clinical value of loss of heterozygosity in serum microsatellite DNA of patients with gastrointestinal stromal tumors.
abstract: OBJECTIVE
  To study the role of loss of heterozygosity (LOH) in serum microsatellite DNA of patients with gastrointestinal stromal tumors (GIST).
  
  
  BACKGROUND
  In GIST, tumor markers from peripheral blood are missing.
  
  
  METHODS
  Seventy-eight patients (59 GIST, 13 leiomyomas, 2 leiomyosarcomas, and 4 schwannomas) underwent resection at our institute between 1985 and 2006. Thirty-three preoperative sera (26 GIST and 7 non-GIST) and 62 postoperative sera (47 GIST and 15 non-GIST) were available and tested for alterations in 12 representative microsatellite loci on chromosomes 22, 17, 13, 9, and 3, using fluorescence-based automated capillary electrophoresis by ABI Prism. Survival was calculated with Kaplan-Meier plots.
  
  
  RESULTS
  Seventeen out of 26 GIST patients had a positive preoperative serum LOH score (> or =2 LOH, sensitivity 65.4%), and 6 out of 7 non-GIST patients had a negative score (< or =1 LOH, specificity 85.7%, P=0.030, Fisher exact test). Serum LOH in GIST were strongly correlated with Fletcher risk groups (P=0.016, chi test). All metastasized GIST (7/7) showed > or =2 LOH preoperatively. Postoperative sensitivity and specificity of LOH analysis for prediction of relapse in 47 GIST was 75.0% and 64.1%, respectively. After a median observation time of 51.3 months (95% confidence interval, 39.4-61.4), LOH in serum significantly predicted overall survival (P=0.007, log-rank test).
  
  
  CONCLUSIONS
  LOH serum analysis in GIST may play a role as a noninvasive, differential diagnostic, prognostic, and monitoring marker in the clinical routine.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg. schurr@uke.uni-hamburg.de
authors.forename: Paulus G
authors.initials: PG
authors.lastname: Schurr
authors.forename: Despoina
authors.initials: D
authors.lastname: Oikonomou
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.forename: Petra
authors.initials: P
authors.lastname: Merkert
authors.forename: Stefan
authors.initials: S
authors.lastname: Wolter
authors.forename: Helge
authors.initials: H
authors.lastname: Kleinhans
authors.forename: Uta
authors.initials: U
authors.lastname: Reichelt
authors.forename: Oliver
authors.initials: O
authors.lastname: Mann
authors.forename: Karim A
authors.initials: KA
authors.lastname: Gawad
authors.forename: Tim
authors.initials: T
authors.lastname: Strate
authors.forename: Emre F
authors.initials: EF
authors.lastname: Yekebas
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D004273:DNA, Neoplasm / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D007889:Leiomyoma / Q000175:diagnosis / Q000235:genetics; D007890:Leiomyosarcoma / Q000175:diagnosis / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009442:Neurilemmoma / Q000175:diagnosis / Q000235:genetics; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D015996:Survival Rate; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm