Analysis of APC/beta-catenin genes mutations and Wnt signalling pathway in desmoid-type fibromatosis.
OBJECTIVE
The abnormalities of the Wnt signalling pathway in desmoid-type fibromatosis were analysed, with the purpose of exploring the mechanism of tumorigenesis and progression.


METHODS
The clinical and histopathological features of 96 cases were analysed. Beta-catenin, cyclin-D1, c-myc, and Ki-67 proteins were detected in 69 cases using formalin-fixed, paraffin-embedded tissues. Using the same materials, apoptosis of the tumour cells was investigated by terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL) testing. Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC) assay, and sequencing were performed to detect abnormalities of the adenomatous polyposis coli (APC) and beta-catenin genes.


RESULTS
APC gene mutations were found in 18 cases (26.1%, 18/69). Somatic mutations of codon 41 in exon 3 of beta-catenin were detected in 13 cases (18.8%, 13/69). No correlation of beta-catenin abnormal expression with the mutations of APC gene or beta-catenin gene was identified (p>0.05). The cases with abnormal beta-catenin expression showed a higher level of c-myc protein expression (69.7%, 23/33) than those without (22.2%, 8/36, p = 0.001). The apoptotic indices (AIs) were significantly lower in cyclin-D1 positive cases and c-myc positive cases (p = 0.015, p = 0.007).


CONCLUSIONS
There are somatic mutations of the APC and beta-catenin gene in desmoid-type fibromatosis, and there are abnormalities in the Wnt signalling pathway. These abnormalities may result in aberrant cell proliferation and apoptosis, which are likely to be important factors in tumorigenesis and progression.
Jilong
Yang
Y
Department of Bone and Soft Tissue Tumor, Cancer Hospital, Tianjin Medical University. Tianjin, China. jilongyang2003@yahoo.com.cn
Jian
Wang
W
Xiaoyan
Zhou
Z
Xiaoqiu
Li
L
Xiongzeng
Zhu
Z
D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D019938:Cyclin D1 / Q000378:metabolism; D018222:Desmoid Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D009154:Mutation; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics*
D019394:Ki-67 Antigen; D016271:Proto-Oncogene Proteins c-myc; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1