Immunohistochemical evaluation of potential molecular targets of desmoid-type fibromatosis

Abstract

Desmoid-type fibromatosis is locally aggressive tumor rare in general population, although commonly present in patients with familial adenomatous polyposis, significantly contributing to the morbidity and mortality of patients. To optimize and individualize the management of patients it is necessary to better understand the biology of these tumors. Immunohistochemical analysis of β-catenin, VEGF, hormone receptors ERβ, ERα and PR, COX-2, APC protein, EGFR, c-kit (CD117), bcl-2 and HER2 expression, potential therapeutic targets, was carried out on 15 archival biopsy samples together with APC gene mutational screening. β-catenin expression was found in all samples, with over 73% showing high range positivity, however with no prognostic significance. Non-specific cytoplasmic localization of β-catenin was observed FAP-associated cases lacking CTNNB1 mutations. Hormone receptor status demonstrated expression of ERβ in 93% of lesions, without detectable ERα or PR. Distinct COX-2 expression of variable intensity was present in all but one desmoid-type fibromatosis case. All lesions demonstrated intense VEGF positivity. Immunoreactivity for the APC protein was found only in 4 cases associated with FAP. No EGFR, HER2, bcl-2 or c-kit expression was detected in any sample. Expression of β-catenin, VEGF, ERβ, COX-2 in high number of cases suggests a potential as future therapeutic targets in desmoid-type fibromatosis.