The Enigma of Desmoid Tumors

Lewis, Jonathan J.; Boland, Patrick J.; Leung, Denis H. Y.; Woodruff, James M.; Brennan, Murray F.

doi:10.1097/00000658-199906000-00014

Cited by 301 publications

(224 citation statements)

References 31 publications

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“…Although some tumors exhibit a significant tendency for local recurrence even in the setting of negative microscopic margins, others do not recur after R1 resection, and some have been observed to spontaneously regress even without therapeutic intervention. 2,46 This interdesmoid tumor heterogeneity suggests the possibility of underlying biological differences; however, relevant molecular prognostic markers are essentially unknown. As has also been observed by others 37,39,40,44 ( Table 5), we have shown that desmoid CTNNB1 mutational spectra are quite limited.…”

Section: Discussionmentioning

confidence: 99%

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Lazar

Tuvin

Hajibashi

et al. 2008

The American Journal of Pathology

405

367

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Desmoid fibromatosis is a rare, nonmetastatic neoplasm marked by local invasiveness and relentless recurrence. Molecular determinants of desmoid recurrence remain obscure. ␤-Catenin deregulation has been commonly identified in sporadic desmoids although the incidence of CTNNB1 (the gene encoding ␤-catenin) mutations is uncertain. Consequently, we evaluated the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoids and examined whether mutation type was relevant to desmoid outcome. Desmoid specimens (195 tumors from 160 patients, 1985 to 2005) and control dermal scars were assembled into a clinical data-linked tissue microarray. CTNNB1 genotyping was performed on a 138-sporadic desmoid subset. Immunohistochemical scoring was performed per standard criteria and data were analyzed using Kaplan-Meier and other indicated methods. CTNNB1 mutations were observed in 117 of 138 (85%) of desmoids. Three discrete mutations in two codons of CTNNB1 exon 3 were identified: 41A (59%) , 45F (33%) , and 45P (8% , excluded from further analysis because of rarity). Five-year recurrence-free survival was significantly poorer in 45F-mutated desmoids (23% , P < 0.0001) versus either 41A (57%) or nonmutated tumors (65%). Nuclear ␤-catenin expression was observed in 98% of specimens and intensity was inversely correlated with incidence of desmoid recurrence (P < 0.01). In conclusion, CTNNB1 mutations are highly common in desmoid tumors. Furthermore, patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may especially benefit from adjuvant therapeutic approaches. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Lazar

Tuvin

Hajibashi

et al. 2008

The American Journal of Pathology

405

367

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“…Desmoid tumours are locally aggressive, non-metastasising tumours [9,13,15,22]. Not only are they rare, they also have an unpredictable clinical course, which makes their treatment difficult.…”

Section: Discussionmentioning

confidence: 99%

“…These tumours are nonencapsulated, infiltrative and locally aggressive [13,22]. However, they lack the cytological features of malignancy and have essentially no metastatic potential [5,9,11,16]. Depending on the site and type of resection, the reported local recurrence rates range from 15 to 77% [4,12,17,19,20,22].…”

Section: Introductionmentioning

confidence: 99%

The management of extra-abdominal desmoid tumours

Duggal

Dickinson

Sommerville

et al. 2004

International Orthopaedics (SICOT)

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We performed a retrospective analysis of 35 cases of desmoid tumours (aggressive fibromatoses) that underwent treatment at our institutions between 1987 and 2002. The purpose was to evaluate the rate of local recurrence of desmoid tumours treated with surgical excision, to assess the impact of surgical margins on local recurrence and to define the role of radiotherapy in the treatment. Nine patients experienced a recurrence at an average of 16 months after initial treatment. Seven of the 15 patients with a less-than-wide margin had a local recurrence. Comparatively, only two of the 20 patients with a wide margin had a local recurrence. Thirty-three of the 35 patients were disease free at the last follow-up. We recommend wide excision with clear margins whenever possible. Marginal resections are appropriate when wide excision would severely compromise the function of the limb. Surgical resections and selective supplementation of adjuvant radiotherapy give excellent control rates.Résumé Nous avons exécuté une analyse rétrospective de 35 cas de tumeurs desmoides (fibromatose agressive) traitées dans notre institution entre 1987 et 2002. Le but était d'évaluer le taux de récidive locale après traitement par excision chirurgicale, d'étudier le rôle des marges chirurgicales sur la récidive et de définir le rôle de la radiothérapie dans le traitement. Neuf malades ont eu une récidive à une moyenne de 16 mois après le traitement initial. Sept des 15 malades opérés avec une marge qui n'était pas large, avait une récidive locale. Comparativement, seulement 2 des 20 malades avec une marge large avaient une récidive locale. Trente trois des 35 malades étaient sans maladie au dernier suivi. Nous recommandons l'excision large avec des marges claires toutes les fois que possible. Les résections marginales sont appropriées quand l'excision large compromettrait sévèrement la fonction du membre. Les résections chirurgicales avec, sélectivement, un traitement adjuvant par radiothérapie donnent d'excellents taux de contrôle de la maladie.

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“…They invade surrounding viscera and neurovascular structures, which may cause significant morbidity and mortality (Lewis et al, 1999). The aggressive growth pattern and their tendency for recurrence make these tumours difficult to treat.…”

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confidence: 99%

Invasion and MMP expression profile in desmoid tumours

et al. 2004

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Desmoid tumours are locally invasive soft tissue tumours in which b-catenin mediated TCF-dependent transcription is activated. The role of soluble factors secreted by the myofibroblastic desmoid tumour, which could stimulate tumour invasiveness, was investigated. Using collagen gel invasion assays, the presence of factors stimulating invasion in desmoid conditioned media (CM) could be established. Since matrix metalloproteinases (MMPs) have been implicated in the process of tumoral invasion, the expression levels of the MMP family members were evaluated. Quantitative reverse transcription -PCR was used to determine the expression levels of MMP1, MMP2, MMP3, MMP7, MMP11, MMP12, MMP13, MMP14 and the inhibitors TIMP1, TIMP2 and TIMP3. Besides overexpression of MMP7, a known TCF-dependent target gene, a striking upregulation of the expression levels of MMP1, MMP3, MMP11, MMP12 and MMP13 in desmoid tumours, compared to unaffected fibroblasts from the same patients, was found. Treating the CM of desmoids with a synthetic and a physiologic MMP inhibitor reduced the invasion-stimulating capacity of the desmoid CM by approximately 50%. These results suggest the involvement of soluble factors, released by the desmoid cells, in stimulating invasion and implicate the MMPs as facilitators of invasion.

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The Enigma of Desmoid Tumors

Cited by 301 publications

References 31 publications

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

The management of extra-abdominal desmoid tumours

Invasion and MMP expression profile in desmoid tumours

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