title: Significance of loss of heterozygosity of the RB1 gene during tumour progression in well-differentiated liposarcomas.
abstract: Tumour progression can be investigated in liposarcomas showing a transition from a low-grade well-differentiated (WD) to a high-grade dedifferentiated (DD) variant. As RB1 gene alterations are common defects in sarcomas, this study examined the frequency of RB1 loss of heterozygosity (LOH) in a group of 14 well-differentiated liposarcomas (WDLs) and 17 well-differentiated/dedifferentiated liposarcomas (WD/DDLs), using a microdissection approach (PALM laser pressure catapulting) that allows the two histological components to be separated for polymerase chain reaction (PCR) analysis. In addition, RB1 protein expression and the Mib1 proliferation index were determined by immunohistochemistry and interphase FISH was performed with an RB1 probe at 13q14. By the use of four intragenic polymorphic RB1 markers (introns 1, 17, 20, and 25) for PCR, allelic losses were found only in the DD parts, but never in the pure WDLs or in the WD components of the WD/DDLs investigated. Furthermore, DD areas characterized by a heterogeneous RB1 protein expression pattern (35-65% immunopositivity), as compared with 90-100% RB1 positivity in WD areas, showed a marked increase in Mib1 proliferation index (19.6% versus 1.8% in WD areas; p<0.001). Interphase fluorescence in situ hybridization (FISH) detected a higher RB1-LOH rate in the DD components of WD/DDLs. Considering the different detection sensitivities of the three methodologies, it is concluded that loss of RB1 function already begins in the WDL, and that the tumour cell population with RB1-LOH starts prevailing in the tumour mass during progression of a WDL.
authors.affiliation: Department of Pathology, Otto-von-Guericke University, 39120 Magdeburg, Leipziger Strasse 44, Germany. regine.schneider-stock@medizin.uni-magdeburg.de
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
authors.forename: Carsten
authors.initials: C
authors.lastname: Boltze
authors.forename: Viola
authors.initials: V
authors.lastname: Jaeger
authors.forename: Marcus
authors.initials: M
authors.lastname: Stumm
authors.forename: Christiane
authors.initials: C
authors.lastname: Seiler
authors.forename: Janusz
authors.initials: J
authors.lastname: Rys
authors.forename: Karin
authors.initials: K
authors.lastname: Schütze
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D002454:Cell Differentiation; D002455:Cell Division; D018450:Disease Progression; D005260:Female; D016161:Genes, Retinoblastoma; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008080:Liposarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein