Genetic instability in primary leiomyosarcoma of bone

Abstract

Primary leiomyosarcoma (LMS) of bone is an exceedingly rare entity on which to date no molecular data have been reported. In a series of 6 tumors (5 grade IIB, 1 grade IIA), we assessed the prevailing genetic stability by microsatellite analysis at 7 loci. The IIB tumors demonstrated a rate of genomic loss as high as 90%, accompanied by an intratumoral heterogeneity in 30% of conspicuous markers. High microsatellite instability in the severe type was not observed, although hMLH1 immunostaining was consistently negative. We assume that intraosseous LMS pertains to “deletor phenotype” tumors. We did observe a locus-specific MSI in our marker linked with hMSH2. Immunostaining and allelotyping indicated a knock-out of pRb in all cases, confirming its major role in sarcomas. Only the stage IIB tumors (4 of 5) pointed to p53 inactivation. In addition, the human telomerase subunit-linked markers exhibited high rates of chromosomal loss. The stage IIA tumor still confined to the bone displayed no genetic instability. Moreover, the proliferation index made a clear distinction between the IIA and IIB tumors (5% vs 30%). We propose to further investigate the usefulness of loss of heterozygosity as a progression marker in this entity.