[951] Immunohistochemical (IHC) Study of Wilms' Tumor Gene 1 (WT1) in Angiomyolipoma (AML) of the Kidney: Dual Role in Tumorigenesis?

R Rawson, DE Westfall, MB Amin, RS Parakh, BL Balzer. Cedars-Sinai Medical Center, Los Angeles, CA

Background: AML has a unique immunophenotype with co-expression of melanocytic markers such as HMB-45 and Melan-A as well as muscle-specific actin. To fully understand the scope of WT1 expression, which has been recently reported in melanocytic tumors as well as in uterine smooth muscle neoplasms, we studied its expression in AML, which has not been evaluated to date. The role of WT1 in tumorigenesis is controversial, as it may act as either a transcriptional activator at the carboxyl (C) terminus or a repressor at the amino (N) terminus based on splices in its transcript. It is hypothesized that WT1 may influence the mesenchymal-epithelial state of cells, thus it may prove helpful in understanding the histogensis and phenotypic characteristics of this triphasic tumor. Monophasic variants of AML, such as epithelioid and leiomyomatous types, may compound the diagnostic dilemma and WT1 may prove useful in this scenario.
Design: We tested 58 renal AMLs (52 classic histology, 2 epithelioid variants and 4 leiomyomatous variants) with WT1 (N-terminal amino acids, Mouse Monoclonal Clone: 6F-H2, Dako) and WT1 carboxyl (C-terminal amino acids, Rabbit Polyclonal Clone: C-19, Santa Cruz Biotechnology) immunohistochemistry.
Results: WT1 was positive in five of 58 cases (4 leiomyomatous AML, 1 epithelioid AML). WT1 carboxyl was positive in six of 58 cases (3 leiomyomatous AML, 1 epithelioid AML, 2 classic AML). Three cases, all leiomyomatous AML, were positive for both WT1 and WT1 carboxyl. When WT1 and WT1 carboxyl positivity was observed, it was seen most frequently in spindled areas, rarely in epithelioid areas and never in adipocytic areas.
Conclusions: 1) The expression of WT1 in the leiomyomatous variant of AML is intriguing, as melanoma-associated markers are more commonly associated with the epithelioid morphology of AML and pure epithelioid AML. 2) WT1 may have utility in diagnosing rare monomorphic variants of AML. 3) WT1 positivity in AML expands the list of tumors that express this marker. 4) WT1 expression was positive for both WT1 N terminus and C terminus antibodies in AML, which highlights the pro- and anti-differentiation functions of this gene as reported in the literature. This further supports that WT1 may be involved in maintaining the mesenchymal-epithelial balance in cells and its activation or suppression may aid in understanding the triphasic morphology unique to this tumor.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 86, Wednesday Morning


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