The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Elizabeth A. Montgomery - One of the best experts on this subject based on the ideXlab platform.
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nuclear beta catenin expression distinguishes deep Fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions
The American Journal of Surgical Pathology, 2005Co-Authors: Baishali Bhattacharya, Cyril Fisher, Harrison Parry Dilworth, Christine A Iacobuziodonahue, Francesca Ricci, Kristin Weber, Mary Furlong, Elizabeth A. MontgomeryAbstract:Nuclear beta-catenin expression distinguishes deep Fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions Deep fibromatoses (desmoid tumors) are clonal myofibroblastic proliferations that are prone to aggressive local recurrences but that do not metastasize. They must be distinguished from a host of fibroblastic and myofibroblastic lesions as well as from smooth muscle neoplasms. Virtually all deep fibromatoses have somatic beta-catenin or adenomatous polyposis coli (APC) gene mutations leading to intranuclear accumulation of beta- catenin. Since low-grade sarcomas in general lack P-catenin and since reactive proliferations would not be expected to have it, we predicted that nuclear beta-catenin expression would be detected in deep fibromatoses but absent in other entities in the differential diagnosis. We evaluated the role of beta- catenin to help differentiate distinguish deep fibromatoses from congeners. Formalin-fixed, paraffin-embedded sections from 21 lesions from 20 patients with deep fibromatoses were stained with monoclonal beta-catenin antibody (Transduction Laboratories) and compared with low-grade fibromyxoid sarcoma (n = 12), leiomyosarcoma (n = 10), various other fibrosarcoma variants (n = 13, including 3 myofibrosarcomas, 3 sclerosing epithelioid fibrosarcomas, 5 low-grade fibrosarcomas, I classic fibrosarcoma arising in dermatofibrosarcoma protuberans, I inflammatory myxohyaline tumor/myxoinflammatory fibroblastic sarcoma), myofibroma/myoFibromatosis (n = 12), nodular fasciitis (n = 11), and scars (n = 9). Nuclear and cytoplasmic staining was assessed. All 21 examples of deep Fibromatosis displayed nuclear beta-catenin (focal nuclear staining in one case to 90% staining). All other lesions tested (n = 67) lacked nuclear labeling for beta-catenin, showing only cytoplasmic accumulation. beta-Catenin immunohistochemistry separates deep Fibromatosis from entities in the differential diagnosis, a finding that can be exploited for diagnosis. Most fibromatoses have diffuse nuclear staining although occasional examples only focally label.
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nuclear beta catenin expression distinguishes deep Fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions
The American Journal of Surgical Pathology, 2005Co-Authors: Baishali Bhattacharya, Cyril Fisher, Harrison Parry Dilworth, Christine A Iacobuziodonahue, Francesca Ricci, Kristin Weber, Mary Furlong, Elizabeth A. MontgomeryAbstract:Deep fibromatoses (desmoid tumors) are clonal myofibroblastic proliferations that are prone to aggressive local recurrences but that do not metastasize. They must be distinguished from a host of fibroblastic and myofibroblastic lesions as well as from smooth muscle neoplasms. Virtually all deep fibromatoses have somatic beta-catenin or adenomatous polyposis coli (APC) gene mutations leading to intranuclear accumulation of beta-catenin. Since low-grade sarcomas in general lack beta-catenin and since reactive proliferations would not be expected to have it, we predicted that nuclear beta-catenin expression would be detected in deep fibromatoses but absent in other entities in the differential diagnosis. We evaluated the role of beta-catenin to help differentiate distinguish deep fibromatoses from congeners. Formalin-fixed, paraffin-embedded sections from 21 lesions from 20 patients with deep fibromatoses were stained with monoclonal beta-catenin antibody (Transduction Laboratories) and compared with low-grade fibromyxoid sarcoma (n=12), leiomyosarcoma (n=10), various other fibrosarcoma variants (n=13, including 3 myofibrosarcomas, 3 sclerosing epithelioid fibrosarcomas, 5 low-grade fibrosarcomas, 1 classic fibrosarcoma arising in dermatofibrosarcoma protuberans, 1 inflammatory myxohyaline tumor/myxoinflammatory fibroblastic sarcoma), myofibroma/myoFibromatosis (n=12), nodular fasciitis (n=11), and scars (n=9). Nuclear and cytoplasmic staining was assessed. All 21 examples of deep Fibromatosis displayed nuclear beta-catenin (focal nuclear staining in one case to 90% staining). All other lesions tested (n=67) lacked nuclear labeling for beta-catenin, showing only cytoplasmic accumulation. beta-Catenin immunohistochemistry separates deep Fibromatosis from entities in the differential diagnosis, a finding that can be exploited for diagnosis. Most fibromatoses have diffuse nuclear staining although occasional examples only focally label.
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beta catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD117 (11 of 11, diffuse) and CD34 (11 of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non-avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (1 of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
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β catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD117 (11 of 11, diffuse) and CD34 (11 of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non-avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (1 of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
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β-Catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:beta-catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the ST1571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the APC/beta- catenin pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD 117 (11 of 11, diffuse) and CD34 (I I of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD 117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non- avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (I of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
Susan C. Abraham - One of the best experts on this subject based on the ideXlab platform.
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beta catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD117 (11 of 11, diffuse) and CD34 (11 of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non-avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (1 of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
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β catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD117 (11 of 11, diffuse) and CD34 (11 of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non-avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (1 of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
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β-Catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:beta-catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the ST1571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the APC/beta- catenin pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD 117 (11 of 11, diffuse) and CD34 (I I of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD 117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non- avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (I of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
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Fibromatosis of the breast and mutations involving the apc β catenin pathway
Human Pathology, 2002Co-Authors: Susan C. Abraham, Elizabeth A. Montgomery, Jae-hyuk Lee, Carol ReynoldsAbstract:Fibromatoses of the breast are nonmetastasizing tumors, but can be infiltrative and locally recurrent. Breast fibromatoses are rare, and their specific genetic alterations have not been elucidated. However, their occasional occurrence in patients with familial adenomatous polyposis (FAP) and their morphologic identification with other deep fibromatoses (desmoid tumors) suggest that alterations of the APC/beta-catenin pathway might be involved in the pathogenesis of sporadic and FAP-associated breast fibromatoses. We analyzed somatic beta-catenin and APC gene mutations in 33 breast fibromatoses (32 sporadic and 1 FAP-associated) using immunohistochemistry for beta-catenin, 5q allelic loss assays, and direct DNA sequencing for exon 3 of the beta-catenin gene and the mutation cluster region of the APC gene. Nuclear accumulation of beta-catenin was present in the stromal tumor cells in most (82%) cases but not in normal stroma or mammary epithelial cells. Somatic alterations of the APC/beta-catenin pathway were detected in 79% of breast fibromatoses, including activating beta-catenin gene mutations in 15 cases and somatic APC alterations (mutation or 5q allelic loss or both) in 11. These findings indicate that alterations of the APC/beta-catenin pathway with resultant nuclear translocation of beta-catenin are important in the pathogenesis of both sporadic and FAP-associated breast Fibromatosis. The spectrum of beta-catenin and APC alterations is similar to that described for desmoid tumors of the abdomen, paraspinal region, and extremities.
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Superficial Fibromatoses are Genetically Distinct from Deep Fibromatoses
Modern Pathology, 2001Co-Authors: Elizabeth Montgomery, Jae-hyuk Lee, Susan C. AbrahamAbstract:Whereas deep fibromatoses (abdominal, extra-abdominal, mesenteric) display locally aggressive behavior, superficial fibromatoses typically remain small and less likely to recur despite essentially identical morphology. Somatic β-catenin or APC gene mutations have been reported in ≤74% of sporadic deep fibromatoses and in virtually 100% of Gardner syndrome–associated fibromatoses, whereas genetic events in superficial fibromatoses remain less well characterized. We performed immunohistochemical staining for β-catenin on 29 superficial fibromatoses (22 palmar, 5 plantar, 1 penile, and 1 infantile digital Fibromatosis) and 5 deep fibromatoses. Mutations of β-catenin and APC genes were analyzed in cases of superficial fibromatoses by direct DNA sequencing of the β-catenin gene on Exon 3 encompassing the GSK-3 36 phosphorylation region and of the APC gene on the mutation cluster region. Nuclear accumulation of β-catenin was present in 86% (25/29) of superficial Fibromatosis cases ranging from 5 to 100% of nuclei (mean, 13%; median, 10%), though in a minority of nuclei in most examples. Deep fibromatoses had 60 to 100% nuclear staining in all five cases. No somatic mutations of β-catenin or APC genes were identified in any of the superficial fibromatoses. In contrast to deep fibromatoses, superficial fibromatoses lack β-catenin and APC gene mutations; the significance of focal nuclear β-catenin accumulation is unclear. This difference may account inpart for their divergent clinical manifestations despite their morphologic resemblance to deep fibromatoses.
Benjamin A Alman - One of the best experts on this subject based on the ideXlab platform.
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β catenin stabilization dysregulates mesenchymal cell proliferation motility and invasiveness and causes aggressive Fibromatosis and hyperplastic cutaneous wounds
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Sophia S Cheon, Raymond Poon, Alexander Y L Cheah, Stefanie Turley, Puviindran Nadesan, Hans Clevers, Benjamin A AlmanAbstract:Fibroproliferative processes are a group of disorders in which there is excessive proliferation of spindle (mesenchymal fibroblast-like) cells. They range from hypertrophic scars to neoplasms such as aggressive Fibromatosis. Cells from these disorders share cytologic similarity with fibroblasts present during the proliferative phase of wound healing, suggesting that they represent a prolonged wounding response. A critical role for β-catenin in mesenchymal cells in fibroproliferative processes is suggested by its high rate of somatic mutation in aggressive Fibromatosis. Using a Tcf-reporter mouse we found that β-catenin protein level and Tcf-transcriptional activity are elevated in fibroblasts during the proliferative phase of healing. We generated a transgenic mouse in which stabilized β-catenin is expressed in mesenchymal cells under control of a tetracycline-regulated promoter. Fibroblasts from the transgenic mice exhibited increased proliferation, motility, and invasiveness when expressing stabilized β-catenin and induced tumors after induction of the transgene when grafted into nude mice. Mice developed aggressive fibromatoses and hyperplastic gastrointestinal polyps after 3 months of transgene induction and healed with hyperplastic cutaneous wounds compared with control mice, which demonstrates an important function for β-catenin in mesenchymal cells and shows a central role for β-catenin in wound healing and fibroproliferative disorders.
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cyclooxygenase two cox 2 modulates proliferation in aggressive Fibromatosis desmoid tumor
Oncogene, 2001Co-Authors: Raymond Poon, Catherine Li, Ron Smits, Shantie Jagmohanchangur, Michael Kong, Sophia S Cheon, Chunying Yu, Riccardo Fodde, Benjamin A AlmanAbstract:Aggressive Fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or β-catenin genes, resulting in β-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in β-catenin stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven Fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2−/− mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to β-catenin stabilization in aggressive Fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion.
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predominance of beta catenin mutations and beta catenin dysregulation in sporadic aggressive Fibromatosis desmoid tumor
Oncogene, 1999Co-Authors: Sabine Tejpar, Friedel Nollet, G Michils, Bharati Bapat, Eric Van Cutsem, Catherine Li, Jay S Wunder, Jean Jacques Cassiman, Benjamin A AlmanAbstract:Aggressive Fibromatosis (also called desmoid tumor) occurs as a sporadic lesion or as part of Familial Adenomatous Polyposis, which is caused by germ line mutations in the Adenomatous polyposis Coli (APC) gene. APC is involved in the regulation of the cellular level of beta-catenin, which is a mediator in Wnt signaling. Mutational analysis of the beta-catenin and APC genes was performed in 42 sporadic aggressive fibromatoses. Nine tumors had mutations in APC, and 22 had a point mutation in beta-catenin at either codon 45 or codon 41 (producing a stabilized beta-catenin protein product). Immunohistochemistry showed an elevated beta-catenin protein level in all tumors, regardless of mutational status. Beta-catenin localized to the nucleus, and was not tyrosine phosphorylated in the six tumors in which this was tested. The demonstration of mutations in two mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin stabilization as the key factor in the pathogenesis of aggressive Fibromatosis. This is the first demonstration of somatic beta-catenin mutations in a locally invasive, but non metastatic lesion composed of spindle cells, illustrating the importance of beta-catenin stabilization in a variety of cell types and neoplastic processes. Moreover, this tumor has one of the highest reported frequencies of beta-catenin mutations of any tumor type.
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adenomatous polyposis coli gene mutation alters proliferation through its β catenin regulatory function in aggressive Fibromatosis desmoid tumor
American Journal of Pathology, 1998Co-Authors: Catherine Li, Bharati Bapat, Benjamin A AlmanAbstract:Aggressive Fibromatosis is a monoclonal proliferation of spindle (fibroblast-like) cells. A subset of lesions contain somatic truncating adenomatous polyposis coli ( APC ) gene mutations, and all of the lesions contain an elevated β-catenin protein level. A major function of APC is to regulate β-catenin protein level. β-Catenin has a dual function in the cell: it is a member of the adherens junction, and it binds transcription factors in the tcf-lef family, transactivating transcription. Cell cultures from aggressive fibromatoses containing an APC mutation were studied. Transient transfection of the full-length APC gene caused decreased proliferation and β-catenin protein level in these cultures. To determine whether β-catenin protein level was responsible for the change in proliferation rate, stable transfections of ΔN89β-catenin (a stabilized form that is not degraded by APC, but retains all other functions) were achieved in half of the cultures derived from each tumor, whereas the other half were transfected with an empty vector. Transfection of the full-length APC gene in cultures that were stably transfected with ΔN89β-catenin did not result in a change in proliferation. The type I promotor of p56lck contains an HMG consensus region, to which members of the tcf-lef family can bind. p56lck was expressed in cultures not transfected with the full-length APC gene and in cultures transfected with the full-length APC gene and ΔN89β-catenin, but not in cultures transfected with only the full-length APC gene. These data show that APC truncating mutations give aggressive Fibromatosis cells a proliferative advantage through β-catenin and suggest that β-catenin acts to transactivate transcription.
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increased beta catenin protein and somatic apc mutations in sporadic aggressive fibromatoses desmoid tumors
American Journal of Pathology, 1997Co-Authors: Benjamin A Alman, Catherine Li, Mandy E Pajerski, Salvador J Diazcano, Hubert J. WolfeAbstract:Sporadic aggressive Fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive Fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues. In some cases, this is caused by a somatic mutation resulting in a truncated APC protein.
Cyril Fisher - One of the best experts on this subject based on the ideXlab platform.
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nuclear beta catenin expression distinguishes deep Fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions
The American Journal of Surgical Pathology, 2005Co-Authors: Baishali Bhattacharya, Cyril Fisher, Harrison Parry Dilworth, Christine A Iacobuziodonahue, Francesca Ricci, Kristin Weber, Mary Furlong, Elizabeth A. MontgomeryAbstract:Nuclear beta-catenin expression distinguishes deep Fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions Deep fibromatoses (desmoid tumors) are clonal myofibroblastic proliferations that are prone to aggressive local recurrences but that do not metastasize. They must be distinguished from a host of fibroblastic and myofibroblastic lesions as well as from smooth muscle neoplasms. Virtually all deep fibromatoses have somatic beta-catenin or adenomatous polyposis coli (APC) gene mutations leading to intranuclear accumulation of beta- catenin. Since low-grade sarcomas in general lack P-catenin and since reactive proliferations would not be expected to have it, we predicted that nuclear beta-catenin expression would be detected in deep fibromatoses but absent in other entities in the differential diagnosis. We evaluated the role of beta- catenin to help differentiate distinguish deep fibromatoses from congeners. Formalin-fixed, paraffin-embedded sections from 21 lesions from 20 patients with deep fibromatoses were stained with monoclonal beta-catenin antibody (Transduction Laboratories) and compared with low-grade fibromyxoid sarcoma (n = 12), leiomyosarcoma (n = 10), various other fibrosarcoma variants (n = 13, including 3 myofibrosarcomas, 3 sclerosing epithelioid fibrosarcomas, 5 low-grade fibrosarcomas, I classic fibrosarcoma arising in dermatofibrosarcoma protuberans, I inflammatory myxohyaline tumor/myxoinflammatory fibroblastic sarcoma), myofibroma/myoFibromatosis (n = 12), nodular fasciitis (n = 11), and scars (n = 9). Nuclear and cytoplasmic staining was assessed. All 21 examples of deep Fibromatosis displayed nuclear beta-catenin (focal nuclear staining in one case to 90% staining). All other lesions tested (n = 67) lacked nuclear labeling for beta-catenin, showing only cytoplasmic accumulation. beta-Catenin immunohistochemistry separates deep Fibromatosis from entities in the differential diagnosis, a finding that can be exploited for diagnosis. Most fibromatoses have diffuse nuclear staining although occasional examples only focally label.
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nuclear beta catenin expression distinguishes deep Fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions
The American Journal of Surgical Pathology, 2005Co-Authors: Baishali Bhattacharya, Cyril Fisher, Harrison Parry Dilworth, Christine A Iacobuziodonahue, Francesca Ricci, Kristin Weber, Mary Furlong, Elizabeth A. MontgomeryAbstract:Deep fibromatoses (desmoid tumors) are clonal myofibroblastic proliferations that are prone to aggressive local recurrences but that do not metastasize. They must be distinguished from a host of fibroblastic and myofibroblastic lesions as well as from smooth muscle neoplasms. Virtually all deep fibromatoses have somatic beta-catenin or adenomatous polyposis coli (APC) gene mutations leading to intranuclear accumulation of beta-catenin. Since low-grade sarcomas in general lack beta-catenin and since reactive proliferations would not be expected to have it, we predicted that nuclear beta-catenin expression would be detected in deep fibromatoses but absent in other entities in the differential diagnosis. We evaluated the role of beta-catenin to help differentiate distinguish deep fibromatoses from congeners. Formalin-fixed, paraffin-embedded sections from 21 lesions from 20 patients with deep fibromatoses were stained with monoclonal beta-catenin antibody (Transduction Laboratories) and compared with low-grade fibromyxoid sarcoma (n=12), leiomyosarcoma (n=10), various other fibrosarcoma variants (n=13, including 3 myofibrosarcomas, 3 sclerosing epithelioid fibrosarcomas, 5 low-grade fibrosarcomas, 1 classic fibrosarcoma arising in dermatofibrosarcoma protuberans, 1 inflammatory myxohyaline tumor/myxoinflammatory fibroblastic sarcoma), myofibroma/myoFibromatosis (n=12), nodular fasciitis (n=11), and scars (n=9). Nuclear and cytoplasmic staining was assessed. All 21 examples of deep Fibromatosis displayed nuclear beta-catenin (focal nuclear staining in one case to 90% staining). All other lesions tested (n=67) lacked nuclear labeling for beta-catenin, showing only cytoplasmic accumulation. beta-Catenin immunohistochemistry separates deep Fibromatosis from entities in the differential diagnosis, a finding that can be exploited for diagnosis. Most fibromatoses have diffuse nuclear staining although occasional examples only focally label.
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beta catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD117 (11 of 11, diffuse) and CD34 (11 of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non-avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (1 of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
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β catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD117 (11 of 11, diffuse) and CD34 (11 of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non-avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (1 of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
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β-Catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis
The American Journal of Surgical Pathology, 2002Co-Authors: Elizabeth A. Montgomery, Michael Torbenson, Manju Kaushal, Cyril Fisher, Susan C. AbrahamAbstract:beta-catenin immunohistochemistry separates mesenteric Fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Although separating gastrointestinal stromal tumor (GIST) from mesenteric Fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the ST1571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the APC/beta- catenin pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric Fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric Fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD 117 (11 of 11, diffuse) and CD34 (I I of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric Fibromatosis had CD 117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non- avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (I of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
Laure Guillou - One of the best experts on this subject based on the ideXlab platform.
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High frequency of β-catenin heterozygous mutations in extra-abdominal Fibromatosis: a potential molecular tool for disease management
British Journal of Cancer, 2010Co-Authors: Julien Domont, S Salas, L Lacroix, D Ranchère, Amélie Neuville, A. Leroux, Veronique Brouste, Patrice Terrier, Patrick Saulnier, Laure GuillouAbstract:Background: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal Fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for β -catenin mutations in a European multicentre series of Fibromatosis tumours to relate β -catenin mutational status to disease outcome. Methods: Direct sequencing of exon 3 β -catenin gene was performed for 155 frozen Fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal Fibromatosis group (101 patients). Results: Mutations of β -catenin were detected in 83% of all cases. Among 101 extra-abdominal Fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with β -catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in β -catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P =0.02). Conclusion: A high frequency (87%) of β -catenin mutation hallmarks extra-abdominal Fibromatosis from a large multicentric retrospective study. Moreover, wild-type β -catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal Fibromatosis.
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high frequency of β catenin heterozygous mutations in extra abdominal Fibromatosis a potential molecular tool for disease management
British Journal of Cancer, 2010Co-Authors: Julien Domont, S Salas, L Lacroix, D Ranchère, Amélie Neuville, A. Leroux, Veronique Brouste, Patrice Terrier, Patrick Saulnier, Laure GuillouAbstract:Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal Fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for β-catenin mutations in a European multicentre series of Fibromatosis tumours to relate β-catenin mutational status to disease outcome. Direct sequencing of exon 3 β-catenin gene was performed for 155 frozen Fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal Fibromatosis group (101 patients). Mutations of β-catenin were detected in 83% of all cases. Among 101 extra-abdominal Fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with β-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in β-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02). A high frequency (87%) of β-catenin mutation hallmarks extra-abdominal Fibromatosis from a large multicentric retrospective study. Moreover, wild-type β-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal Fibromatosis.