Clinical value of loss of heterozygosity in serum microsatellite DNA of patients with gastrointestinal stromal tumors.
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.
Schurr
Paulus G
PG
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg. schurr@uke.uni-hamburg.de
Oikonomou
Despoina
D
Kaifi
Jussuf T
JT
Merkert
Petra
P
Wolter
Stefan
S
Kleinhans
Helge
H
Reichelt
Uta
U
Mann
Oliver
O
Gawad
Karim A
KA
Strate
Tim
T
Yekebas
Emre F
EF
Izbicki
Jakob R
JR
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
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm