CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: A study of 260 desmoid tumors and 191 potential morphologic mimics

Biology-Pathology Medication Department, Institut Claudius Regaud, Toulouse, France.
Modern Pathology (Impact Factor: 6.19). 07/2012; 25(12). DOI: 10.1038/modpathol.2012.115
Source: PubMed


Desmoid tumors are benign monoclonal fibroblastic or myofibroblastic neoplasms, characterized by local invasiveness and high rates of recurrence. Desmoid tumors must be distinguished from benign fibroblastic and myofibroblastic lesions, as well as from low-grade sarcoma, which can appear histologically similar to desmoid tumors. This differential diagnosis can be very difficult, especially when diagnosis is based on a core needle biopsy. On the molecular level, most sporadic desmoid tumors are associated with mutations of the β-catenin gene (CTNNB1). A minority of desmoid tumors are associated with Gardner syndrome and mutations of the familial adenomatous polyposis gene. We identified the common CTNNB1 mutations associated with sporadic desmoid tumors by direct sequencing: in (i) 260 cases of typical desmoid tumors; and (ii) in 191 cases of spindle cell lesions, which can morphologically 'mimic' desmoid tumors. Formalin-fixed paraffin-embedded tissues were obtained via core needle biopsy (n=150) or open biopsy/surgical excision (n=301). Only 16 cases (4%) were not analyzable (Bouin's fixed tissue). CTNNB1 mutations were observed in 223 of 254 (88%) of sporadic desmoid tumors. No CTNNB1 mutations were detected in all other lesions (n=175) studied. CTNNB1 sequencing can be easily and reliably done using tissues obtained via core needle biopsy. Detection of CTNNB1 mutations in formalin-fixed paraffin-embedded tissues among spindle cell lesions is proposed as a specific diagnostic tool for the diagnosis of desmoid tumors. This result has significant implications for patient care and management.Modern Pathology advance online publication, 6 July 2012; doi:10.1038/modpathol.2012.115.

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Available from: Agnès Neuville, Jun 10, 2014
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    • "Mutations in CTNNB1 occur in most AF cases, with the vast majority being one of three point mutations: S45F, T41A, and S45 5,6,8–10. Studies have suggested that the site of the CTNNB1 mutation is associated with differences in clinical behavior of the tumor 6,10,14. "
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    ABSTRACT: Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy.
    Cancer Medicine 02/2014; 3(1). DOI:10.1002/cam4.160 · 2.50 Impact Factor
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    • ". Furthermore, β-catenin (CTNNB1) mutations are reported very frequently [25] [26] [27] [28], although they are absent in DF [22]. These findings indicate that β-catenin plays a rather important role in the tumorigenesis of desmoid tumors. "
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    ABSTRACT: We present a case of desmoplastic fibroma (DF) arising from the right scapula that was incidentally identified by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging performed to evaluate the presence of metastasis due to a history of surgical treatment for endometrioid adenocarcinoma. A 65-year-old woman was admitted to our hospital for consultation about a bone lesion in the right scapula although she was asymptomatic. FDG-PET revealed moderate focal (18)F-FDG uptake in the right scapula with a maximal standardized uptake value of 3.2. The lower angle of the scapula was unclear on plain radiology. Needle biopsy was performed to make a differential diagnosis between primary bone and metastatic tumor. Pathologically, the tumor was composed of a relatively sparse proliferation of spindle-shaped fibroblastic/myofibroblastic cells in a dense collagenous background. Therefore, the diagnosis was a primary fibrous bone tumor. Wide excision was performed, because of the possibility of malignant tumors such as low-grade fibrosarcoma in light of the FDG-PET uptake. Pathologically, the resected tumor was composed of a proliferation of less atypical spindle cells in the collagenous stroma with focally myxoid change; no mitotic figures were observed. Immunohistochemically, β-catenin nuclear/cytoplasmic staining was not observed, and no β-catenin genetic mutations were detected. Therefore, the tumor was diagnosed as DF. DF is a tumor that exhibits FDG-PET uptake. There were no signs of recurrence 6 months after surgery.
    International journal of clinical and experimental pathology 10/2013; 6(10):2230-6. · 1.89 Impact Factor
  • Annales de Pathologie 11/2012; 32(5):S103–S107. DOI:10.1016/j.annpat.2012.07.014 · 0.29 Impact Factor
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