Correlation of oncologic long-term results and genetic instability in soft tissue sarcomas

Purpose: Soft tissue sarcomas (STS) represent a heterotop group of tumours. Microsatellite instabilities (MSI) and loss of heterozygosity (LOH) as phenomena of a genetic instability should be analysed in STS and correlated with the long-term oncologic outcome. Methods: Patients treated for a STS with a follow-up of at least 10 years were included. Thus, 86 patients (mean age 50.5 years, range 16-86 years) treated for a STS between 1993 and 2000 were routinely controlled every 6 months. Incidence of local recurrences, distant metastases, and overall survival were analysed. Sixty-six tumour samples were available for microsatellite analysis using the former traditional method of PCR amplification at 6 loci in the neighbourhood of hMSH2, hMLH1, p53, p16, rb1, and hTR. Results: There were 30 low-grade and 56 high-grade sarcomas. The mean follow-up was 144 months (120-192 months). Twenty-nine patients died of their disease. Local recurrences were seen in 13 patients, whereas metastases were noticed in 23 patients. The overall survival was dependent on the tumour stage (p<0.05), whereas the local tumour control (incidence of local recurrence) was influenced by the surgical margin achieved (p<0.05). The molecular biologic findings revealed 67% of the investigated loci as informative. MSI was found in 6.8% of the informative loci, whereas LOH in 18.8%, respectively. LOH was present in high-grade tumours in 23.8%, whereas in 1.7% in low-grade tumours. In high-grade sarcomas, the 5-year and 10-year survival probabilities were significantly lower in LOH-positive tumours (48.6% and 38%) than in LOH-negative tumours (72.5% and 62%). Conclusion: The overall survival in soft tissue sarcoma is mainly influenced by the tumour stage. In high-grade sarcomas, the survival rate will drop even after 5 years. The detection of loss of heterozygosity represents a negative prognostic predictor in high-grade sarcomas. Microsatellite instability is a rare phenomenon supposing no relevance in the oncogenesis and tumour progression of soft tissue sarcomas.