Cytoplasmic overexpression of WT-1 in gastrointestinal stromal tumor and other soft tissue tumors

The Wilms tumor 1 (WT-1) is a zinc finger transcription factor essential for the development of the kidneys and gonads. Alterations in the WT-1 gene were observed in several tumor types. Depending on the tumor types, WT-1 might function as a tumor suppressor or as a survival factor. WT-1 immunoreactivity in gastrointestinal stromal tumor (GIST) was currently not known. We, therefore, investigated the expression of WT-1 in GIST in comparison to other soft tissue tumors by immunohistochemistry and Western blot analysis. We found that all 28 cases (100%) of GIST are positive for WT-1, diffusely (> 75%, 3+) in 13 (46.4%) cases, moderately (26% to 75%, 2+) in 13 (46.4%) cases, and focally (5% to 25%, 1+) in 2 (7.2%) cases. The staining intensity is usually strong. The staining pattern is predominantly cytoplasmic with rare scattered nuclear staining. Similar but less extensive cytoplasmic WT-1 immunoreactivity was detected in 16 of 25 (64%) uterine leiomyosarcoma and 14 of 24 (58.3%) soft tissue leiomyosarcoma. Rare scattered nuclear staining was also seen in uterine leiomyosarcoma and soft tissue leiomyosarcoma, which showed positive cytoplasmic WT-1 reactivity. Only I of the 10 solitary fibrous tumors showed weak cytoplasmic WT-1 positivity (10%). No WT-1 staining was detected in 6 cases of fibromatosis. The significance of cytoplasmic expression of WT-1 in GIST and some smooth muscle tumors is unclear and warrant further investigation. The potential roles of WT-1 in the diagnosis and treatment of GIST were discussed.