1. ¹Institute of Pathology, Martin Luther University Halle–Wittenberg, Halle, Germany
2. ²Institute of Medical Epidemiology, Biometry and Medical Informatics, Halle, Germany
3. ³Department of Radiotherapy, University of Halle–Wittenberg, Halle, Germany
4. ⁴Institute of Pathology, Department of Gastroenteropathology, Georg-August-University of Göttingen, Göttingen, Germany
5. ⁵Institute of Pathology, Department of Cytopathology, Georg-August-University of Göttingen, Göttingen, Germany
6. ⁶Surgical Clinic, University of Leipzig, Leipzig, Germany

Correspondence: Helge Taubert, Ph.D., Institute of Pathology, Faculty of Medicine, University Halle-Wittenberg, Magdeburger Strasse 14 D-06097 Halle/Saale, Germany; fax: 49-345-5571295; e-mail: helge.taubert@medizin.uni-halle.de

Accepted 15 August 2003.

Abstract

Few studies have investigated the loss of heterozygosity and microsatellite instability in soft tissue sarcomas. Therefore, we analyzed samples of human soft tissue sarcomas to determine the status of the chromosomal region 12q14–15, which contains the MDM2 gene encoding the well-known counterpart of the tumor suppressor p53. In addition, we determined whether an amplified MDM2 gene was present in the samples. Of the 88 soft tissue sarcoma samples, 24 (27%) showed evidence of loss of heterozygosity of markers representing 12q14–15, and 12 (14%) showed evidence of microsatellite instability. Of the 72 samples analyzed by semiquantitative polymerase chain reaction, 15 (21%) possessed an amplified MDM2 gene. Loss of heterozygosity (P = .008) and microsatellite instability (P = .035) were significantly more common in Stage I tumors than in higher stage tumors. This result indicated that these alterations occur early in soft tissue sarcoma progression and possibly define a subgroup of soft tissue sarcoma. Surprisingly, MDM2 amplification in soft tissue sarcoma patients was associated with a prognosis better than that of patients without the amplification; however, this difference was not statistically significant (P = .6). Furthermore, of the tumors with an MDM2 amplification, 40% (6/15) also experienced loss of heterozygosity at 12q14–15; in contrast, only 16% of tumors without an MDM2 amplification (9/57) underwent a loss of heterozygosity. A concomitant occurrence of deletions and amplifications resulting from deficiencies in the nonhomologous end-joining pathway could in part explain this finding.