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1.
Pan Afr Med J ; 39: 211, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34630823

RESUMO

Giant desmoid tumor has been rarely reported in the literature but it is a therapeutic challenge. We here report a case of tumor manifesting as painful abdominal mass causing a major esthetic problem. Radiological assessment allowed to determine its depth extension and limits of resection. Desmoid tumor of the abdominal wall was evoked and surgically resected, with simple outcome. This study highlights challenges in the management of this entity,due to its large size.


Assuntos
Neoplasias Abdominais/diagnóstico por imagem , Parede Abdominal/diagnóstico por imagem , Fibromatose Agressiva/diagnóstico por imagem , Neoplasias Abdominais/patologia , Neoplasias Abdominais/cirurgia , Parede Abdominal/patologia , Parede Abdominal/cirurgia , Feminino , Fibromatose Agressiva/patologia , Fibromatose Agressiva/cirurgia , Humanos , Pessoa de Meia-Idade
2.
J Surg Oncol ; 124(4): 627-634, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34043245

RESUMO

BACKGROUND AND OBJECTIVE: Extra abdominal desmoid tumors are rare, highly aggressive, and invasive benign soft tissue tumors. Current treatment modalities show high levels of recurrence and comorbidities. Cryo-surgery as an alternative was subsequently investigated. METHODS: In this retrospective, single center study 11 patients showing symptomatic tumors were treated with individualized cryo-surgery. Treatment protocol included preoperative planning using computer rendered 3D models, intraoperative navigation and execution using cone beam guidance, and postoperative magnetic resonance imaging image analysis using a gaussian mixture model software. Subjective outcomes were reported using Short Form Health Survey (SF-36) questionnaires. RESULTS: Sixteen ablations were performed, each demonstrating a complete match with the determined preoperative plan and model. A total of 9/11 (82%) of patients showed improvements in symptoms and a reduction in tumor volume while 2/11 (18%) did not. Average reduction in tumor volume and viable segments were 36.7% (p = 0.0397) and 63.3% (p = 0.0477), respectively. Mild complications according to the SIR Adverse Event Classification Guidelines were experienced in 3/16 (19%) ablations. SF-36 scores showed a statistically significant improvement (p = 0.0194) in the mental health category and a nonsignificant (p = 0.8071) improvement in the physical health category. CONCLUSION: Cryo-surgery using the three-phase protocol as described may improve the overall outcome of future ablation procedures.


Assuntos
Criocirurgia/métodos , Fibromatose Agressiva/cirurgia , Carga Tumoral , Adolescente , Adulto , Idoso , Feminino , Fibromatose Agressiva/patologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudo de Prova de Conceito , Estudos Retrospectivos , Adulto Jovem
3.
PLoS One ; 16(4): e0250619, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33914771

RESUMO

Desmoid-type fibromatosis (DF) is a locally aggressive neoplasm characterized by mutations in the CTNNB1 gene, which encodes the ß-catenin protein. We reviewed 85 cases of DF and performed Sanger sequencing for detecting mutations in CTNNB1 and immunostaining for detecting ß-catenin localization. We included 70 DF samples, of which 56 cases demonstrated nuclear ß-catenin localization and 43 cases harboured CTNNB1 mutations. CTNNB1-mutant DF samples consistently displayed nuclear ß-catenin expression and were derived from larger-sized tumours compared to samples with wild-type CTNNB1. When we further classified DF cases into 2 subgroups based on the type of specimen, excised specimens with nuclear ß-catenin expression frequently displayed CTNNB1 mutation and no statistical correlation between nuclear ß-catenin expression and CTNNB1 mutation was observed in biopsies. When we classified CTNNB1 mutation cases into 2 subgroups (DF with T41A or T41I, and DF with S45F or S45P), T41A or T41I mutations were observed more frequently in males than in females. Additionally, DF tumours harbouring S45F or S45P mutations were located more frequently in the abdominal wall than tumours with T41A or T41I mutations. In conclusion, CTNNB1 mutation correlates with nuclear ß-catenin expression in larger or excised DF tumours, and DF harbouring CTNNB1 mutations manifest variable clinical presentations.


Assuntos
Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Mutação , beta Catenina/genética , beta Catenina/metabolismo , Feminino , Fibromatose Agressiva/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
4.
Neurosurgery ; 88(6): 1095-1102, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33556169

RESUMO

BACKGROUND: More effective therapies are needed to treat progressive desmoid tumors when active surveillance and systemic therapy fail. OBJECTIVE: To assess the efficacy and safety of sandwich isolation surgery on the local control of progressive desmoid tumors involving neurovascular bundles. METHODS: A total of 27 patients with progressive desmoid tumors at extremities involving neurovascular bundles who received surgery at our hospital between August 2014 and August 2018 were identified. A total of 13 patients received sandwich isolation surgery, in which R2 resection was performed in neurovasculature-involving regions, and a biomaterial patch was used to envelop involved neurovascular structures and isolate residual tumors. In non-neurovasculature-involving regions, wide resection was performed without isolation. A total of 14 patients received traditional surgery, which included tumor resection without isolation procedure. RESULTS: In sandwich isolation group, tumor progressions and local recurrences occurred in 3 patients outside the isolated neurovasculature-involving regions. However, no progressions or recurrences occurred in any patients in the isolated neurovasculature-involving regions where R2 resection was performed. Sandwich isolation surgery group and traditional surgery group shared similar baseline clinical characteristics. The estimated 3-yr event-free survival rate was 76.9% after sandwich isolation surgery, and 32.7% after traditional surgery (P = .025). Patients who received sandwich isolation surgery were less likely to have local recurrence (hazard ratio: 0.257, P = .040). No complications were noted except intermittent mild pain in operative regions (2 cases). CONCLUSION: Sandwich isolation surgery is effective and safe for local control of desmoid tumors involving neurovascular bundles.


Assuntos
Fibromatose Agressiva/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Adolescente , Adulto , Fibromatose Agressiva/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Intervalo Livre de Progressão , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento
5.
Eur J Cancer ; 145: 109-120, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33444924

RESUMO

Previous studies have not clearly identified a prognostic factor for desmoid tumours (DT). Whole-exome sequencing (WES) and/or RNA sequencing (RNA-seq) were performed in 64 cases of DT to investigate the molecular profiles in combination with the clinicopathological characteristics. CTNNB1 mutations with specific hotspots were identified in 56 cases (87.5%). A copy number loss in chromosome 6 (chr6) was identified in 14 cases (21.9%). Clustering based on the mRNA expression profiles was predictive of the patients' prognoses. The risk score generated by the expression of a three-gene set (IFI6, LGMN, and CKLF) was a strong prognostic marker for recurrence-free survival (RFS) in our cohort. In risk groups stratified by the expression of IFI6, the hazard ratio for recurrence-free survival in the high-risk group relative to the low-risk group was 12.12 (95% confidence interval: 1.56-94.2; p = 8.0 × 106). In conclusion, CTNNB1 mutations and a chr6 copy number loss are likely the causative mutations underlying the tumorigenesis of DT while the gene expression profiles may help to differentiate patients who would be good candidates for wait-and-see management and those who might benefit from additional systemic or radiation therapies.


Assuntos
Biomarcadores Tumorais/genética , Fibromatose Agressiva/genética , Transcriptoma , Adolescente , Adulto , Idoso , Quimiocinas/genética , Pré-Escolar , Cromossomos Humanos Par 6 , Cisteína Endopeptidases/genética , Análise Mutacional de DNA , Feminino , Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/patologia , Fibromatose Agressiva/terapia , Dosagem de Genes , Perfilação da Expressão Gênica , Humanos , Proteínas com Domínio MARVEL/genética , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Mutação , Prognóstico , RNA-Seq , Tóquio , Sequenciamento Completo do Exoma , Adulto Jovem , beta Catenina/genética
6.
J Cancer Res Clin Oncol ; 147(7): 2127-2135, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33452581

RESUMO

PURPOSE: Desmoid fibromatosis (DF) is a locally aggressive connective-tissue tumor arising in deep soft tissues. Although multiple therapeutic modalities have been demonstrated effective for DF, there is no standard systemic treatment for progressive and recurrent DF. As a part of systemic treatment, tyrosine kinase inhibitors have shown promising activity against DF with tolerable toxicity profiles. Thus, the aim of this study was to investigate the efficacy and safety of apatinib, a novel multi-target angiogenesis inhibitor, in patients with DF. METHODS: We retrospectively analyzed the medical records of patients with advanced extremity DF regularly treated with apatinib between October 2017 and January 2020 in our center. Apatinib was initially administered with a dose of 250 mg daily and the dose was adjusted according to the toxicity. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria. The primary endpoint was progression-free survival (PFS); objective response rates and drug-related adverse events were also evaluated. RESULTS: A total of 22 (6 male, 16 female) patients with advanced extremity DF were included. The mean medication time was 17 months. None of the patients reached a complete response, but ten (45.5%) patients achieved partial response, and 11 patients (50%) achieved stable disease. One (4.5%) patient developed progressive disease, and the 1-year PFS rate was 95.2%. The disease control rate was 95.4% (21/22) and the objective response rate was 45.5% (10/22). Meanwhile, 18 (81.8%) patients with a tumor shrinkage were accompanied by a decreased signal intensity of lesions in T2-weighted magnetic resonance imaging. The most frequent adverse events included hand-foot syndrome (n = 7, 31.8%), fatigue (n = 6, 27.2%), local pain (n = 4, 18.1%), diarrhea (n = 4, 18.1%). CONCLUSION: Apatinib is an effective and well-tolerated option for patients with advanced extremity DF. Indeed, further prospective, randomized studies with larger cases are required to fully explore the clinical utility of apatinib in DF.


Assuntos
Antineoplásicos/uso terapêutico , Extremidades/patologia , Fibromatose Agressiva/tratamento farmacológico , Piridinas/uso terapêutico , Adolescente , Adulto , Criança , Feminino , Fibromatose Agressiva/patologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
7.
BMJ Case Rep ; 14(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419745

RESUMO

In the context of a post-treatment testicular germ cell tumour, an abdominal lesion found on surveillance CT studies led to a differential diagnosis, including recurrent germ cell tumour. We report the case of a 48-year-old man who was noted to have a new interval soft tissue lesion on a surveillance CT scan, 5 years after initial orchidectomy and chemotherapy. Excision of this lesion and histopathological review revealed an intra-abdominal desmoid.


Assuntos
Neoplasias Abdominais/diagnóstico por imagem , Neoplasias Abdominais/patologia , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/terapia , Neoplasias Abdominais/cirurgia , Fibromatose Agressiva/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
8.
Diagn Cytopathol ; 49(2): E49-E54, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32857922

RESUMO

Intra-abdominal desmoid fibromatosis (also known as desmoid tumor) is a rare benign but often locally aggressive infiltrative fibrous proliferation. Pancreatic desmoid fibromatosis is even rarer, with only 31 cases previously reported in the English-language literature. These tumors present a distinct diagnostic challenge due to their rarity and non-specific image findings and presentation, with most cases diagnosed as desmoid fibromatosis only after surgical resection. This report presents a rare case of pancreatic desmoid fibromatosis in a 72 year old man, who on a follow-up CT for a previously diagnosed angiomyolipoma of the kidney was found to have a 4.0 cm pancreatic tail mass. This was sampled pre-operatively by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). Examination of the cytology material showed a low-grade spindle cell lesion. Immunohistochemistry (IHC) performed on FNA cell block showed the lesional cells to be positive for beta-catenin, consistent with fibromatosis. Additional mutational analysis on cell block material revealed the characteristic CTNNB1 gene mutation (T41A), confirming the diagnosis. The mass was then surgically resected and again confirmed to be desmoid fibromatosis on histopathologic examination. On review of previously published cases of pancreatic desmoid fibromatosis, most were initially suspected to be some type of pancreatic neoplasm and were not biopsied prior to surgical resection. This case suggests a potential key role for fine-needle aspiration cytology in the preoperative diagnosis of pancreatic and other intra-abdominal desmoid tumors, particularly as evidence emerges that non-surgical treatment may be a viable first option for some cases.


Assuntos
Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Idoso , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Endossonografia/métodos , Fibromatose Agressiva/metabolismo , Humanos , Imuno-Histoquímica/métodos , Masculino , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/metabolismo , beta Catenina/metabolismo
9.
Eur J Surg Oncol ; 47(5): 1196-1200, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32847695

RESUMO

BACKGROUND: Desmoid-Type Fibromatosis (DTF) is a rare mesenchymal neoplasm with a locally invasive pattern and high risk of local recurrence after surgery. Historically, the standard treatment for DTF was surgical resection. However, considering the difficulty of achieving surgical eradication, the possible unnecessary morbidity and the unpredictability of the natural history, a wait-and-see approach has been proposed for asymptomatic DTF. METHODS: We analyzed 87 consecutive patients with histologically-proven sporadic primary DTF, first recurrence or residual disease managed at our institution between 2000 and 2018. Patients and tumor-related variables were reviewed and analyzed. Two different treatment strategies were adopted according to different time periods: in the "early period" (2000-2010) patients underwent surgical treatment irrespective of the clinical presentation, whereas in the "late period" (2012-2018) asymptomatic patients used to undergo a wait-and-see strategy. The event-free survival (EFS) was compared trough a pre-post comparison. RESULTS: In the early period, surgery was performed in 51 (94.4%) patients and watchful waiting in 3 (5.6%). In the late period, the watchful waiting group accounted for 24 (72.7%) patients and the surgical group for 9 (27.3%). No statistically independent prognostic factors were found. EFS did not show statistically significant differences between early and late period groups. CONCLUSION: Wait-and-see policy has shown to be equivalent to upfront surgery in terms of EFS; therefore, a conservative approach is recommended in asymptomatic patients diagnosed with DTF that can be followed through watchful waiting.


Assuntos
Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/cirurgia , Conduta Expectante , Adulto , Idoso , Feminino , Fibromatose Agressiva/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
11.
Gac Med Mex ; 156(5): 439-445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33372933

RESUMO

A literature review on desmoid tumors was carried out, which are tumors that affect soft tissues with a locally aggressive behavior and are unable to metastasize. Sporadic cases are located on the extremities and chest wall; hereditary cases have an intra-abdominal predilection, and those associated with pregnancy occur on the abdominal wall. Imaging techniques assess disease extension. Trucut biopsy is the study of choice for diagnosis. Mutations in the CTNNB1 or APC genes cause an abnormal accumulation of b-catenin within the cell. In this review, an emphasis is made on therapeutic strategies' evolution and change, and current tools for decision making are analyzed, as well as clinical outcomes. Radiation therapy can play a therapeutic or adjuvant role. Advances in the understanding of the disease have allowed establishing better targeted treatments with lower morbidity; however, there are still unanswered questions regarding the choice of the ideal candidate for surveillance and/or early treatment. Data related to quality of life are also presented, as well as the uncertainty generated by this diagnosis for both doctor and patient.


Assuntos
Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/terapia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Biópsia/métodos , Tomada de Decisão Clínica , Feminino , Fibromatose Agressiva/patologia , Humanos , Masculino , Qualidade de Vida , Radioterapia , Incerteza , beta Catenina/metabolismo
12.
J Med Invest ; 67(3.4): 375-377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33148921

RESUMO

Background : Desmoid-type fibromatosis is a very rare disease that has no characteristic image findings, so it is often difficult to differentiate from gastrointestinal stromal tumor (GIST). A case of desmoid-type fibromatosis that was difficult to differentiate from GIST is reported. The decisive factor in the diagnosis was positive nuclear immunostaining for ß-catenin nucleus. Case presentation : A man is his 30s had no significant past medical history, including no abdominal surgery. A medical check-up found a large tumor in the right lateral abdomen. After some examinations, a preoperative diagnosis of GIST was made, and open ileocecal resection was performed. However, the final diagnosis based on the pathological findings was desmoid-type fibromatosis. Conclusions : We should consider desmoid-type fibromatosis when we find a large abdominal mass, but it may be difficult to diagnose based only on imaging findings. Immunohistochemical examination of the specimen may make the diagnosis. J. Med. Invest. 67 : 375-377, August, 2020.


Assuntos
Fibromatose Agressiva/diagnóstico , Neoplasias Gastrointestinais/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Adulto , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Fibromatose Agressiva/patologia , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Tomografia Computadorizada por Raios X
13.
J Cancer Res Ther ; 16(4): 900-902, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930137

RESUMO

Objective: Aggressive fibromatosis (AF), also called desmoid tumor, is an uncommon soft-tissue neoplasm. Characteristically, it expands locally without metastatic potential. However, its tendency of relapse after curative resections has been well documented. Effective treatment options have been limited and there is a clear need for novel treatment strategies. Methods: We used combination therapy including multikinase tyrosine kinase inhibitor for treating AF. Results: We presented a case of an extra-abdominal AF who was successfully treated with meloxicam and sorafenib combination in our clinic. She tolerated this therapy well with only mild side effects. To our knowledge, this is the first case report of an extra-abdominal AF with a major partial response to sorafenib and meloxicam combination. Conclusion: Due to the favorable toxicity profile of sorafenib and meloxicam, this combination might be an effective treatment option for patients with locally aggressive and inoperable AF.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibromatose Agressiva/tratamento farmacológico , Neoplasias Musculares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/patologia , Humanos , Perna (Membro)/patologia , Imageamento por Ressonância Magnética/métodos , Meloxicam/administração & dosagem , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe/administração & dosagem , Resultado do Tratamento
14.
Pediatr Blood Cancer ; 67(10): e28636, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32762028

RESUMO

Systemic therapy for pediatric desmoid tumors has been challenged by a lack of high-quality clinical evidence and potential adverse effects. The gamma-secretase inhibitor nirogacestat has shown promising efficacy in adults. We report four cases of pediatric and young adult desmoid tumor patients (three with familial adenomatous polyposis [FAP] syndrome) who received nirogacestat on compassionate use. After a median of 13.5 months (range 6-18), three had durable benefit: a complete response (Case 1); a partial response (Case 2); stable disease (Case 3). The fourth had disease progression after a partial response. No patient experienced grade 3 or 4 adverse events.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Fibromatose Agressiva/tratamento farmacológico , Tetra-Hidronaftalenos/uso terapêutico , Valina/análogos & derivados , Adolescente , Adulto , Pré-Escolar , Feminino , Fibromatose Agressiva/patologia , Humanos , Masculino , Prognóstico , Segurança , Valina/uso terapêutico , Adulto Jovem
15.
Int J Surg Oncol ; 2020: 9197216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733704

RESUMO

Objectives: Desmoid tumor also called aggressive fibromatosis is a rare type of benign tumor. It is a mesenchymal malignancy without metastatic potential. The standard management is resection, but other options including observation may be discussed. Desmoid-type fibromatosis may occur throughout the body, but the abdominal wall is the most common site. The aim of our study was to assess the clinicoepidemiological profile, prognostic factors, and treatment outcome of desmoid tumors. Methods: A monocentric retrospective study was conducted over a period of 19 years between February 2000 and November 2019 at the oncology department of Salah Azaïz Institute. Our study concerns 30 patients with desmoid tumor. All data regarding patients were obtained from the medical record. Results: Thirty patients were included. The median age was 35 years with a female predominance (sex ratio = 0.07). A palpable mass was the most common complaint (n = 27). Median tumor size was 5 cm. The principal site of involvement was the abdominal wall (n = 14). Surgery was performed in 27 patients. The histopathology reports listed 14 (52%) cases with negative margins and 13 (48%) cases with positive margins. Radiation therapy was performed in 2 patients. One patient received tamoxifen. Local recurrence occurred in 11 patients. Two patients died of their desmoid tumor. Abdominal wall tumors have less risk of recurrence compared with other sites (p=0.047). Macroscopic margin involvement (R2) was the only prognostic factor influencing disease-free-survival (p=0.034). Conclusion: Desmoid tumors are aggressive tumors with a tendency for local recurrence. Abdominal wall tumors have less risk of recurrence. Macroscopic margin involvement was the only prognostic factor that affects disease-free-survival.


Assuntos
Fibromatose Agressiva/patologia , Fibromatose Agressiva/cirurgia , Recidiva Local de Neoplasia , Parede Abdominal/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Intervalo Livre de Doença , Feminino , Fibromatose Agressiva/terapia , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Prognóstico , Radioterapia , Estudos Retrospectivos , Taxa de Sobrevida , Tamoxifeno/uso terapêutico , Adulto Jovem
16.
Oncogene ; 39(34): 5589-5600, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32651460

RESUMO

Wnt/ß-catenin signaling is one of the key cascades regulating embryogenesis and tissue homeostasis; it has also been intimately associated with carcinogenesis. This pathway is deregulated in several tumors, including colorectal cancer, breast cancer, and desmoid tumors. It has been shown that CTNNB1 exon 3 mutations are associated with an aggressive phenotype in several of these tumor types and may be associated with therapeutic tolerance. Desmoid tumors typically have a stable genome with ß-catenin mutations as a main feature, making these tumors an ideal model to study the changes associated with different types of ß-catenin mutations. Here, we show that the apoptosis mechanism is deregulated in ß-catenin S45F mutants, resulting in decreased induction of apoptosis in these cells. Our findings also demonstrate that RUNX3 plays a pivotal role in the inhibition of apoptosis found in the ß-catenin S45F mutants. Restoration of RUNX3 overcomes this inhibition in the S45F mutants, highlighting it as a potential therapeutic target for malignancies harboring this specific CTNNB1 mutation. While the regulatory effect of RUNX3 in ß-catenin is already known, our results suggest the possibility of a feedback loop involving these two genes, with the CTNNB1 S45F mutation downregulating expression of RUNX3, thus providing additional possible novel therapeutic targets for tumors having deregulated Wnt/ß-catenin signaling induced by this mutation.


Assuntos
Neoplasias Abdominais/genética , Polipose Adenomatosa do Colo/genética , Apoptose/genética , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Fibromatose Agressiva/genética , Mutação de Sentido Incorreto , Via de Sinalização Wnt/genética , beta Catenina/genética , Neoplasias Abdominais/metabolismo , Neoplasias Abdominais/patologia , Polipose Adenomatosa do Colo/metabolismo , Polipose Adenomatosa do Colo/patologia , Linhagem Celular Tumoral , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Regulação para Baixo , Fibromatose Agressiva/metabolismo , Fibromatose Agressiva/patologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , beta Catenina/metabolismo
18.
Cancer Sci ; 111(8): 2935-2942, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32539220

RESUMO

This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease desmoid-type fibromatosis. It was designed as a multiinstitutional joint research project with 7 major centers in Japan participating. The committee members of 7 major medical centers specializing in bone and soft tissue tumors formed this study group to develop clinical care guidelines. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathologic prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n = 3), 5-year local recurrence-free survival (LRFS) was 52.9%. No case had received pre- or postoperative radiotherapy. Univariate analysis revealed that extremity location (P < .001) and larger size (8 cm or more, P = .036) were significant adverse risk factors for LRFS. Multivariate analysis indicated that extremity location (P < .001) was a significantly adverse factor in addition to recurrent tumor (P = .041), S45F mutation (P = .028), and R1 surgical margin (P = .039). Preoperative drug treatment, including nonsteroidal antiinflammatory drugs, did not reduce the incidence of local recurrence (P = .199). This is the first study to analyze the factors correlating with outcomes of surgical treatment, including CTNNB1 mutation status, in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Europe and North America. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.


Assuntos
Fibromatose Agressiva/cirurgia , Recidiva Local de Neoplasia/epidemiologia , beta Catenina/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Mutacional de DNA/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Fibromatose Agressiva/genética , Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/patologia , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Fatores de Risco , Adulto Jovem
19.
Cir Cir ; 88(3): 361-365, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538991

RESUMO

Desmoid tumors are clinical entities rarely diagnosed at an initial presentation because of its low incidence, they are characterized by a locally aggressive presentation and high rates of local relapse. Its presentation can be intra- or extra-abdominal. We present a clinical case of a female, 15 year old patient, with three months of abdominal pain, a giant intra-abdominal mass was diagnosed with histologic diagnosis of desmoid tumor. Several surgical procedures were performed, having a las a R1 resection (focally microscopic margins). In this case association with pregnancy, abdominal trauma, previous surgeries and genetic syndromes were discarded.


Assuntos
Neoplasias Abdominais/patologia , Fibromatose Agressiva/patologia , Neoplasias Abdominais/diagnóstico por imagem , Neoplasias Abdominais/cirurgia , Parede Abdominal/cirurgia , Adolescente , Biópsia , Colectomia , Feminino , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/cirurgia , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Cirúrgicos Reconstrutivos , Telas Cirúrgicas , Tomografia Computadorizada por Raios X
20.
Am J Surg Pathol ; 44(9): 1266-1273, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32590455

RESUMO

Desmoid fibromatosis (DF) is a rare, locally aggressive, nonmetastasizing fibroblastic/myofibroblastic tumor with a tendency to recur and an unpredictable clinical course. A "wait-and-see" policy is the new standard of care. DF are characterized by activating alterations of the wnt/ß-catenin pathway: CTNNB1 or adenomatous polyposis coli gene (APC) mutations (these mutations being mutually exclusive). Desmoid-type fibromatosis of the breast (DFB) is rare with an incidence of 0.2% of breast tumors. The diagnosis of DFB is difficult, as it must be distinguished from metaplastic carcinoma and other spindle cell lesions. Sequencing of 128 DFB identified a lower rate of CTNNB1 mutations using Sanger (65.6%) or Sanger+next-generation sequencing (77.7%) and a higher rate of APC mutations (11.8%) than in all-site DF. By excluding patients with familial adenomatous polyposis (n=2), the rate of APC mutations in DFB was high (10.7%). The distribution of CTNNB1 mutations in DFB was different from all-site DF, with a higher rate of T41A (68.9%), a lower rate of S45F (5.7%), and a similar rate of S45T (12.6%). By combining the 2 molecular techniques in a 2-step manner (Sanger, then next-generation sequencing), we increased the detection rate of CTNNB1 mutations and lowered the rate of wild-type tumors from 34.4% to 9.8%, therefore improving the diagnosis of DFB. The identification of the exon 3 CTNNB1 mutation in breast spindle cell lesions is a highly specific tool for the diagnosis of DFB, in addition to extensive immunohistochemical analysis. Our study also underlines the importance of APC in DFB tumorigenesis. These findings have significant implications for patient care and management.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama Masculina/genética , Neoplasias da Mama/genética , Fibromatose Agressiva/genética , Mutação , beta Catenina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/terapia , Feminino , Fibromatose Agressiva/patologia , Fibromatose Agressiva/terapia , França , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Fenótipo , Prognóstico , Adulto Jovem
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