APC and beta-catenin in alveolar soft part sarcoma (ASPS)--immunohistochemical and molecular genetic analysis.
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.
Kuhnen
C
C
Institute of Pathology, University Hospital Bergmannsheil, Bochum, Germany. patho-bhl@ruhr-uni-bochum.de
Herter
P
P
Monse
H
H
Kahmann
S
S
Muehlberger
T
T
Vogt
P M
PM
Steinau
H U
HU
Müller
K M
KM
Müller
O
O
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
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin