Expression of Wilms' tumor gene (WT1) is associated with survival in malignant pleural mesothelioma.

INTRODUCTION: Calretinin and Wilms' tumor gene (WT1) are mesothelial markers routinely used to confirm the diagnosis of malignant pleural mesothelioma (MPM). We investigated the prognostic value of calretinin and WT1 expression in predicting survival in a series of patients diagnosed with MPM in our institution. MATERIALS AND METHODS: Fifty-two patients diagnosed of MPM were retrospectively reviewed. Calretinin and WT1 were stained for IHC analysis in formalin-fixed, paraffin-embedded sections and positivity was considered for tumors with >1 % of tumor cells stained. Survival data were calculated by the Kaplan-Meier method and Cox regression was used to evaluate the prognostic value of the variables. RESULTS: Calretinin IHC expression was positive in 83.7 % of patients and WT1 in 78.1 %. A significant association of calretinin and WT1 expression with epithelial histology was detected (p = 0.030 and p = 0.010). We found a significant increase in OS in patients with epithelial subtype, PS1 and neutrophil-lymphocyte ratio (NLR) ≤5 (p < 0.05). In the IHC markers analysis, we found a significant increase in OS for patients with WT1 positive expression (16.4 vs. 2.3 m, p = 0.013), but not differences for calretinin expression (16.6 vs. 5.0 months, p = 0.37). In the multivariate analysis, epithelial histology and WT1 remained as significant prognostic factors for survival (p = 0.004 and p = 0.010, respectively). CONCLUSION: In our series of 52 MPM patients, epithelial histology, PS, NLR and WT1 expression are significant prognostic factors for survival. We concluded that WT1, but not calretinin, is a useful prognostic factor in MPM. The role of WT1 assessment is worth of prospective validation in future studies on MPM.

A new morphological variant of uterine PEComas with sex-cord-like pattern and WT1 expression: more doubts about the existence of uterine PEComas.

PEComas are rare neoplasms that are sometimes associated with the tuberous sclerosis complex. They typically contain perivascular epithelioid cells that coexpress muscle and melanocytic markers. However, apart from these classical features, considerable clinical, pathologic, and immunohistochemical variation has been reported. WT1, the Wilms tumor gene product, can be expressed in various tumors from different anatomical sites, including sex-cord and other ovarian tumors with a sertoliform pattern. Neither a sex-cord-like pattern nor WT1 expression has been described in PEComas. Here, we describe a case of uterine PEComa with a pattern of infiltration into the myometrium that is similar to stromal sarcomas, characterized by tongues and endovascular growing. The architecture and cellular morphology were similar to sex-cord tumors, and the PEComa was diffusely and strongly positive for WT1. We reviewed, from our files, an additional 9 cases of PEComa from different sites, and found WT1 expression in one more soft tissue tumor. We discuss the relationship between PEComas and other uterine sarcomas.

Prognostic significance of WT1 gene expression in pediatric acute myeloid leukemia.

BACKGROUND: The Wilms Tumor gene (WT1) encodes a transcription factor involved in kidney development and malignancy. WT1 expression in a subpopulation of early CD34+ cells has suggested its involvement in hematopoiesis. WT1 is aberrantly expressed in leukemias. High expression of WT1 at diagnosis has been associated with unfavorable prognosis in adult acute myeloid leukemia (AML). The prognostic relevance of WT1 expression in pediatric AML was evaluated in only one study, including 47 patients, which showed that very low levels of WT1 at presentation were associated with an excellent outcome. To test the validity of these findings we measured levels of WT1 in 41 newly diagnosed pediatric AML of the non-M3 FAB subtype. PROCEDURE: Patients were treated according to an AML-BFM 83-based protocol in a single institution. Mononucleated cells obtained from presentation BM aspirates were cryopreserved and later thawed and used for total RNA extraction and cDNA synthesis. The quantitative assessment of WT1 transcripts was made by real-time PCR (RQ-PCR). WT1 transcripts values were normalized with respect to the number of ABL transcripts. RESULTS: WT1 levels were significantly higher in patients bearing favorable chromosome abnormalities, t(8;21) and inv(16) (P = 0.002). Higher levels of WT1 expression were unexpectedly associated with a higher probability of overall survival by Cox regression analysis (P = 0.002). Multivariate regression analysis could not discriminate between the effects of WT1 and cytogenetics on survival. CONCLUSIONS: Higher WT1 expression was associated with favorable cytogenetics subtypes and accordingly with better outcome in children with AML in this study.