Aims: Wilms' tumour-1 (WT-1) encodes a transcription factor originally identified as a tumour suppressor gene, whose mutations are responsible for tumorigenesis of Wilms' tumour. The overexpression of WT-1 has been demonstrated in variable tumours. In this study, WT-1 immunoreactivity was explored in 97 gastrointestinal stromal tumours (GISTs).
Methods: The expression of WT-1 was compared with other immunohistochemical markers of GIST and the association with clinicopathological features was also evaluated. For comparison, six melanomas and 71 soft tissue tumours were used.
Results: All 97 GISTs were positive for WT-1 and the staining intensity was strong in 59 (60.8%), moderate in 28 (28.9%) and weak in 10 cases (10.3%). Cytoplasmic staining with moderate to strong intensity was more frequent in GISTs positive for platelet-derived growth factor receptor-alpha (PDGFRA) (p = 0.04). However, WT-1 immunoreactivity was not related to the clinicopathological variables, including tumour location, histological subtype, risk of progression and recurrence status. Leiomyosarcomas, schwannomas, malignant peripheral nerve sheath tumours (MPNSTs) and melanomas showed cytoplasmic staining, whereas leiomyomas and mesenteric fibromatoses were totally negative for WT-1.
Conclusions: Although the biological roles of WT-1 in GIST are still unknown, our findings might provide a rationale for immunotherapy targeting WT-1 and a therapeutic solution to the challenge of imatinib-resistant GISTs.