Beta-catenin in soft tissue sarcomas: expression is related to proliferative activity in high-grade sarcomas.
Besides its role in cell adhesion, beta-catenin exerts a function as an oncoprotein. The aim of this study was the characterization of its expression, possible mutation, and the assessment of beta-catenin as a prognostic indicator for soft tissue sarcomas. A total of 115 soft tissue sarcomas were analyzed using immunohistochemistry, immunogold-electron microscopy, and DNA analysis. Information from 56 patients was available for follow-up. A statistically significant correlation was found between intracellular distribution of beta-catenin and the proliferative activity (MIB-1 expression) in high-grade sarcomas (P = .0008). Beta-catenin was identified with intracytoplasmic and nuclear accumulation, showing additional membranous staining in sarcomas with epithelioid pattern. Ultrastructurally, a colocalization between beta-catenin and nuclear heterochromatin was demonstrated. In 22 analyzed tumors, only one (yet undescribed) mutation of the beta-catenin gene (C-A transversion) could be detected. Prognostic validity of the cellular expression of beta-catenin, however, was not proven. Apart from its membranous function as an effective molecule for cell-adhesion in sarcomas with epithelioid pattern, beta-catenin may act as an oncoprotein in sarcomas with intracytoplasmic and nuclear localization with binding to nuclear DNA. A previously discussed stimulation of cell proliferation caused by an increased beta-catenin level can also be postulated for high-grade soft tissue sarcomas in correlation with the rate of proliferation. Mutations of the beta-catenin gene are probably of lesser importance for the accumulation of beta-catenin in soft tissue sarcomas.
Kuhnen
C
C
Institute for Pathology, Limb Tumor Registry, University Hospital Bergmannsheil, Bochum, Germany. patho-bhl@ruhr-uni-bochum.de
Herter
P
P
Müller
O
O
Muehlberger
T
T
Krause
L
L
Homann
H
H
Steinau
H U
HU
Müller
K M
KM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear; D001483:Base Sequence; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006046:Gold; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D011379:Prognosis; D012509:Sarcoma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling; D015534:Trans-Activators; D051176:beta Catenin
D034961:Antigens, Nuclear; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D015534:Trans-Activators; D051176:beta Catenin; D006046:Gold