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Microsatellite DNA Alterations of Gastrointestinal Stromal Tumors Are Predictive for Outcome

Authors' Affiliations: ¹ Department of General, Visceral, and Thoracic Surgery and ² Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Requests for reprints: Paulus Schurr, Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. Phone: 49-40-42803-2401; Fax: 49-40-42803-4995; E-mail: schurr{at}uke.uni-hamburg.de.

Purpose: In gastrointestinal stromal tumors (GIST), loss of heterozygosity (LOH) on chromosome 22 and its presumptive biological function has been described. The prognostic value of these and other DNA regions for patient survival remains unclear.

Experimental Design: Sixty patients who underwent surgery at our institution between 1992 and 2003 for GIST were histopathologically reclassified by immunohistochemistry and the GIST consensus group criteria 2001. Twenty-one microsatellite loci on chromosomes 3, 9, 13, 17, 18, and 22 were screened for alterations in tumor and healthy DNA. Survival was calculated by Kaplan-Meier plots.

Results: Eleven (18.3%) of 60 patients showed metastases at presentation. Thirteen (21.7%) of 60 were high-risk GISTs. LOH was found in all tumors. Twenty-eight (46.7%) of 60 showed more than two LOH in 21 microsatellite marker sites. The frequency of single marker LOH varied from 1.7% to 28.3% among tumors. Frequent LOH was found on chromosomes 22 and 17. The correlation of LOH positivity and the consensus scoring was significant (P = 0.005, ² test). After a median observation time of 33.3 months (95% confidence interval, 23.9-42.6), overall survival was best for patients with tumors of very low, low, and intermediate risks with only 6 of 36 death events, whereas 14 of 24 high-risk and metastasized patients had died (P < 0.001, log-rank test). Likewise, LOH significantly predicted survival (P = 0.013) and the effect was particularly detrimental for LOH on chromosome 17 (P < 0.001).

Conclusions: LOH is a useful phenomenon for the prognosis of GIST. Rather than chromosome 22 markers, chromosome 17 markers independently predict survival.