APC and β-catenin in alveolar soft part sarcoma (ASPS) - immunohistochemical and molecular genetic analysis

Summary Apart from its role in cell-adhesion, s-catenin is regarded as an oncoprotein, the cytoplasmic level of which is regulated by APC as a tumor suppresser 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 s-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. s-Catenin showed a partly membranous, partly strong intracytoplasmic expression. No gene mutations for APC and s-catenin were detected in any of the four cases. These investigations suggest that, apart from their function in carcinogenesis and fibromatoses, APC and s-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 suppresser protein has not yet been investigated. A nuclear function of APC in ASPS in down-regulating nuclear transcription processes linked to overexpression of s-catenin, as is known in colorectal carcinogenesis, may be hypothesized.