Prognostic significance of WT1 expression in soft tissue sarcoma
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RESEARCH
WORLD JOURNAL OF SURGICAL ONCOLOGY
Open Access
Prognostic significance of WT1 expression in soft tissue sarcoma Ahrong Kim1, Eun Young Park2, Kyungbin Kim3, Jeong Hee Lee3, Dong Hoon Shin2,3, Jee Yeon Kim2,3, Do Youn Park1,2, Chang Hun Lee1,2, Mee Young Sol2,3, Kyung Un Choi2,3*, Jeung Il Kim4 and In Sook Lee5
Abstract Background: Soft tissue sarcomas (STS) are rare. We evaluated the WT1 protein expression level in various types of STS and elucidated the value of WT1 as a prognostic factor and a possible therapeutic target. Methods: Immunohistochemical staining for WT1 was performed in 87 cases of STS using formalin-fixed, paraffin-embedded blocks. The correlation between WT1 expression and clinicopathological factors was analyzed. Survival analysis was conducted in 67 patients. We assessed the validity of WT1 immunohistochemistry as an index of WT1 protein expression using Western blot analysis. Results: WT1 expression was noted in 47 cases (54.0%). Most rhabdomyosarcomas and malignant peripheral nerve sheath tumors showed WT1 expression (91.7% and 71.4%, respectively; P = 0.005). WT1 expression was related to higher FNCLCC histologic grade and AJCC tumor stage. In the group with high grade STS, strong WT1 expression was correlated with better survival (P = 0.025). The immunohistochemical results were correlated quantitatively with the staining score and the concentration of the Western blot band. Conclusions: This study demonstrates that various types of STS show positive immunostaining for WT1 and that WT1 expression has a prognostic significance. So STS should be considered candidates for WT1 peptide–based immunotherapy.
Background The Wilms’ tumor gene (WT1) located at chromosome 11p13 was originally identified as a tumor-suppressor gene associated with Wilms’ tumor, a kidney neoplasm of childhood. The WT1 is mutated in the germline of children with a genetic predisposition to Wilms’ tumor and is inactivated in a subset of sporadic Wilms’ tumors [1-3]. The WT1 gene encodes a zinc-finger transcription factor, which regulates target genes, some of which are related to cell differentiation, proliferation, and apoptosis, and binds to specific sequences within the promoter regions of the WT1 gene itself. It also binds to a number of other genes, such as insulin like growth factor-II, platelet-derived growth factor A chain, and IGH-I receptor [4-8]. The WT1 gene also has a central * Correspondence: [email protected] 2 Department of Pathology, School of Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea 3 Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam-do 626-770, Republic of Korea Full list of author information is available at the end of the article
role in embryonic development [9] and is normally expressed in a limited set of tissues, including gonad, uterus, kidney, and mesothelium [10-12]. Recent studies have suggested that WT1 has an important role not only as a tumor suppressor, but also as a tumor promoter in v
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