WT-1 expression in gastrointestinal stromal tumours.
OBJECTIVE
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.
Kang
Gu-Hyun
GH
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim
Kyoung-Mee
KM
Noh
Jae-Hyung
JH
Sohn
Tae-Sung
TS
Kim
Sung
S
Park
Cheol-Keun
CK
Lee
Choong-Sik
CS
Kang
Dae-Young
DY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D025721:WT1 Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D025721:WT1 Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha