The remaining 15 tumors were reclassified based on morphology, additional immunohistochemistry and fluorescence in situ hybridization as desmoid-type fibromatosis (3 tumors), nerve sheath/neural tumors (3 tumors), low-grade fibromyxoid sarcoma, medallion-like dermal fibroma, poorly differentiated Sertoli cell tumor, nodular/proliferative fasciitis, calcifying fibrous tumor, aneurysmal bone cyst of soft tissue, STAT6-negative SFT with adipocytic differentiation, undifferentiated small round blue cell tumor, and scar (1 tumor each).
Only few studies address other signaling pathways which can drive uncontrolled growth in DTF such as: JAK/STAT, Notch, PI3 kinase/AKT, mTOR, Hedgehog, and the estrogen growth regulatory pathways.
The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased.
In addition to the CTNNB1 mutation (64%), pediatric AF showed AKT1 (31%), BRAF (19%), and TP53 (9%) mutations, whereas only the CTNNB1 mutation was found in adult AF.
CTNNB1, APC, AKT1, BRAF TP53, and RET Sanger sequencing and next-generation sequencing (NGS) with the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2 were performed on formalin-fixed samples from 28 pediatric and 33 adult AFs.
In addition to the CTNNB1 mutation (64%), pediatric AF showed AKT1 (31%), BRAF (19%), and TP53 (9%) mutations, whereas only the CTNNB1 mutation was found in adult AF.
In agreement with these results, S100a4 appears to be co-expressed together with mesenchymal stem cell (MSC) markers in desmoid tumours from Apc<sup>1638N/+</sup> mice, as well as from sporadic and hereditary human desmoids.
Our data provide the first report on the in vivo role of S100a4 in intestinal tumourigenesis and describe a new role for S100a4 in the aetiology of desmoids formation.
Recently, two distinct stromal signatures derived from a macrophage response (colony-stimulating factor 1, CSF1) and a fibroblastic response (desmoid-type fibromatosis, DTF) were identified in breast carcinomas and correlated with clinicopathologic features including outcome.
A role for the serine to phenylalanine substitution at codon 45 (the S45F mutation) in the catenin (cadherin-associated protein) β-1 (CTNNB1) gene as a molecular predictor of local recurrence in patients with primary, sporadic desmoid tumor (DT) has been reported.
A role for the serine to phenylalanine substitution at codon 45 (the S45F mutation) in the catenin (cadherin-associated protein) β-1 (CTNNB1) gene as a molecular predictor of local recurrence in patients with primary, sporadic desmoid tumor (DT) has been reported.
An initial screen of gene expression data for 48 RTKs in 148 sarcomas showed that ROR2 was expressed in a subset of leiomyosarcoma (LMS), gastrointestinal stromal tumour (GIST) and desmoid-type fibromatosis (DTF).
Interestingly, enhanced midkine expression significantly correlated with a higher propensity and decreased time for primary DT recurrence (log-rank p = 0.0025).
The correlation between β-catenin aberrant expression and VEGF overexpression was examined and microvessel density (MVD) assessed by immunohistochemical expression of CD31 in 74 samples (63 primary and 11 recurrent samples, 63 patients) of sporadic desmoid tumours without familial adenomatous polyposis (FAP).
There was a statistically significant correlation between widespread nuclear expression of β-catenin and overexpression of VEGF in all desmoid tumours (P = 0.04, Fisher's exact test).