Article
Lab Invest 2001, 81:833–844
Rb and TP53 Pathway Alterations in Sporadic and NF1-Related Malignant Peripheral Nerve Sheath Tumors
Sarah Birindelli1, Federica Perrone1, Maria Oggionni1, Cinzia Lavarino1, Barbara Pasini2, Barbara Vergani1, Guglielmina N Ranzani4, Marco A Pierotti3 and Silvana Pilotti1
- 1Pathology and Cytopathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
- 2Preventive Medicine Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
- 3Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
- 4Department of Genetics and Microbiology, University of Pavia, Pavia, Italy
Correspondence: Dr. Silvana Pilotti, Unita' di Anatomia e Istologia Patologica e Citopatologia, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via G. Venezian, 1, 20133 Milano, Italy. E-mail: pilotti@istitutotumori.mi.it
Received 12 February 2001.
Abstract
Karyotypic complexities associated with frequent loss or rearrangement of a number of chromosome arms, deletions, and mutations affecting the TP53 region, and molecular alterations of the INK4A gene have been reported in sporadic and/or neurofibromatosis type I (NF1)-related malignant peripheral nerve sheath tumors (MPNSTs). However, no investigations addressing possible different pathogenetic pathways in sporadic and NF1-associated MPNSTs have been reported. This lack is unexpected because, despite similar morphologic and immunophenotypic features, NF1-related cases are, by definition, associated with NF1 gene defects. Thus, we investigated the occurrence of TP53 and p16INK4A gene deregulation and the presence of microsatellite alterations at markers located at 17p, 17q, 9p21, 22q, 11q, 1p, or 2q loci in MPNSTs and neurofibromas either related (14 cases) or unrelated (14 cases) to NF1. Our results indicate that, in MPNSTs, p16INK4A inactivation almost equally affects both groups. However, TP53 mutations and loss of heterozygosity involving the TP53 locus (43% versus 9%), and p53 wild type overexpression, related or not to mdm2 overexpression (71% versus 25%), seem to mainly be restricted to sporadic MPNSTs. In NF1-associated MPNSTs, our microsatellite results are consistent with the occurrence of somatic inactivation by loss of heterozygosity of the second NF1 allele.
