Beta-catenin accumulation and gene mutation in exon 3 in dedifferentiated liposarcoma and malignant fibrous histiocytoma.
BACKGROUND
beta-Catenin is an adhesion molecule that also plays a role in the Wnt signaling pathway. Objective.-To analyze beta-catenin mutation and accumulation in a series of liposarcomas and malignant fibrous histiocytomas.


METHODS
beta-Catenin mutation in exon 3 was studied using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis in 30 formalin-fixed, paraffin-embedded liposarcomas. The tumors included 12 dedifferentiated liposarcomas, characterized by both high-grade anaplastic components and well-differentiated liposarcoma components, plus 18 well-differentiated liposarcomas (10 lipoma-like and 8 sclerosing-type cases). The 2 components of dedifferentiated liposarcomas were analyzed independently. beta-Catenin accumulation in the nuclei or cytoplasm and Ki-67 expression (cell-proliferation marker, MIB-1 labeling index) were examined immunohistochemically. Nine storiform-pleomorphic-type malignant fibrous histiocytomas were also studied.


RESULTS
Dedifferentiated liposarcomas showed mutation in 2 cases (17%) and accumulation in 5 cases (42%). One of the 2 cases that showed mutations had a mutation in the well-differentiated component; this mutation was silent. The other case had mutations that differed between the 2 components. In well-differentiated liposarcomas, mutation was not seen in any of the cases (0/18; 0%); however, accumulation was seen frequently in the sclerosing-type cases (5/8; 63%), but not in the lipoma-like cases (0/10; 0%). Malignant fibrous histiocytomas showed mutation and accumulation in 5 (56%) and 4 (44%) cases, respectively, without any exact correlation between the cases. Cases with accumulation had a higher MIB-1 labeling index than those without, among both the sclerosing-type well-differentiated liposarcomas (P <.05) and the malignant fibrous histiocytomas.


CONCLUSIONS
Our results suggest the possible involvement of beta-catenin activation caused by beta-catenin mutation in liposarcoma and malignant fibrous histiocytoma, but the contribution would seem to be different, depending on the tumor type. beta-Catenin accumulation is also thought to be related to cell proliferation in some of the cases.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Akio
A
Sakamoto
Yoshinao
Y
Oda
Toshisada
T
Adachi
Tsuyoshi
T
Saito
Sadafumi
S
Tamiya
Yukihide
Y
Iwamoto
Masazumi
M
Tsuneyoshi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004210:Dissection / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008846:Micromanipulation; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D015534:Trans-Activators; D051176:beta Catenin