Abstract
Introduction
Desmoid-type fibromatosis (DF) are locally infiltrative, non-metastasizing tumours associated with significant morbidity and mortality if located intra-abdominally, retroperitoneally or in head and neck localisation. They are mostly sporadic, due to somatic CTNNB1 mutations. Alternatively, they can be associated with germline pathogenic variants in APC causing Familial Adenomatous Polyposis (FAP). Germline APC variants and somatic CTNNB1 mutations are mutually exclusive.
Aims and methods
We conducted a retrospective descriptive analysis of patients with DF seen at the Royal Marsden NHS Foundation Trust Sarcoma Unit in London. We aimed to describe the methods of screening for FAP in patients with DF from a specialist unit. Patients diagnosed between 1992 and 2020 were selected from the prospectively maintained Sarcoma Unit database.
Results
226 patients were identified and 67% (n = 152) were female. Median age at diagnosis was 37.5 (range 2–81) years. Tumour localisation was limbs/pelvis in 30.9% (N = 70), intra-abdominal 16.8% (N = 38), abdominal wall 23.5% (N = 53), thorax 18.6% (N = 42), head and neck 3.1% (N = 7) and vertebral/paravertebral 7.1% (N = 16). Colonoscopy was requested in 65 patients (28.8% of all cases) and was completed in forty-six (20.4%). Molecular testing of CTNNB1 testing was requested in 35 cases (15.5%). APC germline test was requested in 12 cases. Four patients in our cohort had an FAP-associated DF.
Conclusions
CTNNB1 ± APC testing and colonoscopy are useful tools for the screening of patients with DF. CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. Negative CTNNB1 results, alongside clinical assessment, should prompt APC testing and/or colonoscopy.
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References
Ross J, Zhang X (2013) Desmoid-type fibromatosis. Atlas Genet Cytogenet Oncol Haematol. 17(8):571–578
De Marchis M, Tonelli F, Quaresmini D, Lovero D, Della-Morte D, Silvestris GF et al (2017) Desmoid tumours in familial adenomatous polyposis. Anticancer Res 37:3357–3366
Church J, Xhaja X, Laguardia L, O’Mallet M, Burke C, Kalady M (2015) Desmoids and genotype in familial adenomatous polyposis. Dis Colon Rectum 58:444–448
Kattentidt Mouravieva AA, Geurts-Giele I, De Krijger R, Van Noesel M, van de Ven C et al (2012) Identification of familial adenomatours polyposis carriers among children with desmoid tumours. Eur J Cancer 48:1867–1874
Bui N, Kummar S (2017) Molecular insigths into desmoid tumours. Editorial. Oncotarget 8(53):90608–90609
Akiyama T (2000) Wnt/neta-catenin signalling. A mini review. Cytokine Growth factors Reviews 11:273–282
Tejpar S, Michils G, Denys H, Van Dam K et al (2005) Analysis of Wnt/beta catenin signalling in desmoid tumours. Acta Gastro-Enterologica Belgica 68:5–9
Gao C, Wang Y, Broaddus R, Sun L, Xue F, Zhang W (2018) Exon 3 mutations of CTNNB1 drive tumorigenesis: a review. Oncotarget 9(4):5492–5508
Lazar A, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E et al (2008) Specific mutations in beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumours. The American Journal of Pathology. https://doi.org/10.2353/ajpath.2008.080475
Colombo C, Miceli R, Lazar A, Perrone F, Pollock R, Cesne LE, A, et al (2013) CTNNB1 45F mutation is a molecular prognosticator of increased postoperative primary desmoid tumour recurrence. Cancer 119:3696–3702
Hamada S, Futamura N, Ikuta K, Urakawa H, Kozawa E, Ishigura N, Nishida Y (2014) CTNNB1 S45F mutation predicts poor efficacy of meloxicam treatment for desmoid tumours: A pilot study. PLoS ONE. https://doi.org/10.1371/journal.pone.0096391
Mullen J, Delaney T, Rosenberg A, Le L, Iafrate AJ, Kobayashi W et al (2013) Beta-catenin mutations status and outcomes in sporadic desmoid tumours. Oncologist 18:1043–1049
Domont J, Salas S, Lacroix L et al (2010) High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management. Br J Cancer 102:1032–1036
Jasperson K, Tuohy T, Neklason D, Burt R (2010) Hereditary and familial colon cancer. Gastroenterology 138(6):2044–2058
Ikenoue T, Yamaguchi K, Komura M, Imoto S, Yamaguchi R et al (2015) Attenuated familial adenomatours polyposis with desmoids caused by an APC mutation. Human Genome Variation 2:15011
Brensinger JD, Laken SJ, Luce MC, Powell SM, Vance GH et al (1998) Variable phenotype of familial adenomatous polyposis in pedigrees with 3’ mutations in the APC gene. Gut 43:548–552
Sinha A, Tekkis PP, Gibbons DC, Phillips RK, Clark SK (2011) Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis. Colorectal Dis 13:1222–1229
Gurbuz AK, Giardiello FM, Petersen GM et al (1994) Desmoid tumours in familial adenomatous polyposis. Gut 35(3):377–381. https://doi.org/10.1136/gut.35.3.377
Wang WL, Nero C, Pappo A, Lev D, Lazar AJ, López-Terrada D (2012) CTNNB1 genoty** and APC screening in pediatric desmoid tumors: a proposed algorithm. Pediatr Dev Pathol. 15(5):361–367. https://doi.org/10.2350/11-07-1064-OA.1
Koskenvuo L, Ristimäki A, Lepistö A (2017) Comparison of sporadic and FAP-associated desmoid-type fibromatoses. J Surg Oncol 116(6):716–721. https://doi.org/10.1002/jso.24699
Clark SK, Phillips RK (1996) Desmoids in familial adenomatous polyposis. Br J Surg 83(11):1494–1504. https://doi.org/10.1002/bjs.1800831105
Shin R, Cho H-S, Kim D-W, Ahn S, Ihn M, Park H et al (2017) Does routine colonoscopy help diagnose familial adenomatous polyposis in patients presenting with desmoid tumours but no gastrointestinal symptoms? Int J Colorectal Dis 32:151–154
Shenbagaraj L, Thomas-Gibson S, Stebbing J et al (2019) Endoscopy in 2017: a national survey of practice in the UK. Frontline Gastroenterology 10:7–15
National Genomic Test Directory. Testing Criteria for Rare and Inherited Disease. Draft March 2019. Available from https://www.england.nhs.uk/publication/national-genomic-test-directories/, accessed 20-Jun-20
Talseth-Palmer BA (2017) The genetic basis of colonic adenomatous polyposis syndromes. Hereditary Cancer in Clinical Practice 15:5. https://doi.org/10.1186/s13053-017-0065-x
Kerr S, Thomas C, Thibodeau N, Ferber M, Halling K (2013) APC Germline mutations in individuals being evaluated for familial adenomatous polyposis. A review of the Mayo Clinic experience with 1591 consecutive tests. The Journal of Molecular Diagnosis. https://doi.org/10.1016/j.jmoldx.2012.07.005
The Desmoid Tumour Working Group (2020) The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer 127:96–107. https://doi.org/10.1016/j.ejca.2019.11.013
Acknowledgements
R L Jones: Receipt of grants/research support: MSD, GSK. Receipt of consultation fees: Adaptimmune, Athenex, Blueprint, Boehringer- Ingelheim, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immunedesign, Lilly, Merck, Pharmamar, UptoDate. T P McVeigh: Receipt of grants and honoraria from Roche, Novartis, Astra Zeneca/MSD, Blackrock Clinic, Hermitage Medical Clinic and Galway Clinic.
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Conceptualization: EC, TMcV. Data curation: EC, SG, TMcV. Supervision: TMcV, RJ, CB, MS, AH, DS. Writing—original draft: EC, TMcV. Writing—review & editing: all authors
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Institutional approval for use of the data was sought through the service evaluation that was approved (SE964, date 24/05/2020) by the Royal Marsden Institutional Review Board.
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Because this was a retrospective study, written informed consent was not obtained from the subjects. At Royal Marsden Hospital, for retrospective clinical studies such as case reports and treatment effects, we confirm with patients the consent for comprehensive clinical studies. All participants in this study agree on its comprehensive research participation.
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Cojocaru, E., Gennatas, S., Thway, K. et al. Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK. Familial Cancer 21, 69–74 (2022). https://doi.org/10.1007/s10689-021-00230-8
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DOI: https://doi.org/10.1007/s10689-021-00230-8