title: APC and beta-catenin in alveolar soft part sarcoma (ASPS)--immunohistochemical and molecular genetic analysis.
abstract: Apart from its role in cell-adhesion, beta-catenin is regarded as an oncoprotein, the cytoplasmic level of which is regulated by APC as a tumor suppressor protein. Changes of chromosome 5q, the region that includes the APC-gene, are known to be important in the pathogenesis of fibromatosis; however, little is known about the significance of APC and beta-catenin in other mesenchymal tumors. Therefore, we used immunohistochemistry and DNA-analysis to investigate four cases of alveolar soft-part sarcoma (ASPS) as a mesenchymal tumor with a distinct histologic appearance. In three cases of ASPS the APC-gene product was found to have strong nuclear expression and only faint cytoplasmic staining. Beta-catenin showed a partly membranous, partly strong intracytoplasmic expression. No gene mutations for APC and beta-catenin were detected in any of the four cases. These investigations suggest that, apart from their function in carcinogenesis and fibromatoses, APC and beta-catenin play a role in the pathogenesis of soft tissue tumors such as ASPS. The significance of a striking nuclear accumulation of non-mutated, virtually functionally active APC-tumor suppressor protein has not yet been investigated. A nuclear function of APC in ASPS in down-regulating nuclear transcription processes linked to overexpression of beta-catenin, as is known in colorectal carcinogenesis, may be hypothesized.
authors.affiliation: Institute of Pathology, University Hospital Bergmannsheil, Bochum, Germany. patho-bhl@ruhr-uni-bochum.de
authors.forename: C
authors.initials: C
authors.lastname: Kuhnen
authors.forename: P
authors.initials: P
authors.lastname: Herter
authors.forename: H
authors.initials: H
authors.lastname: Monse
authors.forename: S
authors.initials: S
authors.lastname: Kahmann
authors.forename: T
authors.initials: T
authors.lastname: Muehlberger
authors.forename: P M
authors.initials: PM
authors.lastname: Vogt
authors.forename: H U
authors.initials: HU
authors.lastname: Steinau
authors.forename: K M
authors.initials: KM
authors.lastname: Müller
authors.forename: O
authors.initials: O
authors.lastname: Müller
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000328:Adult; D001132:Arm / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D006801:Humans; D007866:Leg / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin