Droplet Digital PCR (ddPCR) as a Novel Technology in Detecting CTNNB1 Mutations in Desmoid Fibromatosis

• Published in: Applied immunohistochemistry & molecular morphology Vol. 30; no. 10; p. 662
• Main Authors: Gandhi, Jatin, Kao, Erica, Wu, Yu, Mantilla, Jose G, Ricciotti, Robert W, Bandhlish, Anshu, Liu, Yajuan J, Chen, Eleanor Y
• Format: Journal Article
• Language: English
• Published: United States 01.11.2022
• Subjects: beta Catenin - genetics; beta Catenin - metabolism; Fibromatosis, Aggressive - diagnosis; Fibromatosis, Aggressive - genetics; Fibromatosis, Aggressive - pathology; Humans; Mutation; Polymerase Chain Reaction; Technology
• ISSN: 1533-4058
• DOI: 10.1097/PAI.0000000000001076

Desmoid fibromatosis (DF) is a locally aggressive soft tissue neoplasm with frequent recurrences. DF is characterized by alterations in the Wnt/β-catenin pathway, with the majority showing sporadic mutations in CTNNB1 , whereas others have germline mutations in APC . Immunohistochemical staining for β-catenin is often difficult to interpret and can be negative in up to 30% of cases. Prior studies have shown that some DFs lacking nuclear expression of β-catenin may carry activating CTNNB1 mutations. Droplet digital polymerase chain reaction (ddPCR) has been used effectively in detecting mutations in formalin-fixed, paraffin-embedded (FFPE) samples of various cancer types. In this study, we assess the diagnostic utility of ddPCR to detect CTNNB1 mutations in DF with β-catenin expression on immunohistochemistry (IHC), as well as in diagnostically challenging cases. Of the 28 DFs with nuclear β-catenin expression by IHC, 24 cases showed a CTNNB1 mutation by ddPCR using primers against the most common point mutations in CTNNB1 . The most frequent mutation was T41A (n=14; 50%), followed by S45F (n=8; 33%) and S45P (n=3;12%). We identified 8 additional (myo)fibroblastic lesions of uncertain classification, which were negative for nuclear β-catenin expression by IHC. We detected CTNNB1 mutations in 3 unknown lesions, including S45F (n=2) and S45P (n=1). ddPCR is a sensitive, rapid and cost-efficient methodology to detect common CTNNB1 mutations in DF, especially in diagnostically challenging cases.