Frameshift mutations of ubiquitination-related genes HERC2, HERC3, TRIP12, UBE2Q1 and UBE4B in gastric and colorectal carcinomas with microsatellite instability.

Similarly, Ben-Izhak et al. reported two cases of fibromatosis following radiation therapy for Hodgkin’s lymphoma. Although these observations indicate that irradiation may play a role in the appearance of desmoid-type fibromatosis, even after a long interval, the efficacy of radiation therapy for their treatment has never been challenged. Beside familial syndromes, sporadic desmoid-type fibromatosis is associated with somatic mutations of CTNNB1 that occur specifically within exon 3 in more than 80% of tumours. Although such mutations are often reported in epithelial cancers, they are not observed in reactive fibroblastic processes. CTNNB1mutations lead to nuclear accumulation of b-catenin that can be detected by immunohistochemistry. In this study, we failed to detect any significant nuclear expression of b-catenin despite the presence of a specific mutation in exon 3 of CTNNB1. This lack of nuclear expression suggests that this CTNNB1 mutation may not be associated with an activated protein and therefore is of questionable biological significance. However, Amary et al. reported that in a large series of desmoid-type tumours, nuclear expression of b-catenin was absent in a foot tumour that harboured a CNNTB1 mutation. Moreover, b-catenin expression has been reported to be focal in several cases. Although desmoid-type fibromatosis does not metastasise, the prognosis is conditioned by frequent recurrences, especially in patients with the Ser45Phe mutation in exon 3 of CTNNB1. These patients should receive appropriate follow-up. In summary, this case study is important because it addresses the problem of a discordance between genotype and phenotype, an issue that is becoming more and more central in the routine clinical activity as molecular techniques are now frequently associated with the classical histological methods for the diagnosis of rare diseases, such as desmoid-type fibromatosis. Specifically, b-catenin immunodetection, which has been reported to be sometimes negative or difficult to interpret, is of relative (moderate) importance and the diagnosis of desmoid-type fibromatosis can be established based on histopathological criteria. Moreover, the CTNNB1 mutation, although characteristic of this lesion, is not 100% specific as described also in other tumours (e.g., endometroid adenocarcinomas). The biological significance of molecular data, particularly when they seem to be in disagreement with the histological results (in our case a CTNNB1 mutation not associated with typical histological features), must be interpreted only in relation to the clinical context. Indeed, the history of the patient and the radiological aspect of deep malignant tumour with infiltrative pattern were the most important criteria that, in the presence of a CTNNB1 mutation (which has never been reported in benign processes), indicated a desmoid-type fibromatosis rather than a benign fibroblastic process. Caroline Rouleau*{{ Hélène Vernhet§ Marion Marty Isabelle Hostein Pierre Alricjj Jean Michel Coindre