Prognostic Impact of WT1 Protein Expression on Overall Survival in De-Novo Acute Myeloid Leukemia (AML) with Normal Cytogenetics
Sarah-Joy Haggstrom, Payam Pournazari, Farid Kosari, Meer-Taher Shabani-Rad, Jay Patel, Iwona Auer, Joanne Luider, Thomas Fourie, Doug Demetrick, Michelle Geddes, Jan Storek, Adnan Mansoor. University of Calgary/Calgary Laboratory Services (CLS), Calgary, AB, Canada; University of Calgary, Calgary, AB, Canada; Universtiy of Calgary, Calgary, AB, Canada
Background: Dysregulation of the Wilms tumor 1 gene (WT1) by mutations and/or over expression is relatively frequent in AML and plays' a role in blast proliferation and impaired differentiation. Over expression of WT1 mRNA in AML is associated with poor prognosis on GEP. The prognostic impact of WT1 mutations in cytogenetically normal (CN) AML was recently reported (Blood 2009). Anti WT1 antigen specific T-cells, exert potent anti-tumor activity and WT1 antigen as “tumor vaccination” is being evaluated with promising results in initial trials. The clinical significance of WT1 protein is not known. We studied WT1 by IHC in a cohort of de-novo AML with normal cytogenetics and correlated it with clinical outcome.
Design: Diagnosis was based on WHO (2008) criteria; utilizing morphology, flow-cytometry and cytogenectics +/- FISH. Triplicate cores of diagnostic BM biopsy tissue (FFPE) was used to create TMA. Sections (4 μM) were stained (CD34/WT1/ CD117/ MPO) according to standard protocol. WT1 staining was scored (0,1,2,3,) based on intensity and score >0 was considered positive. Kaplan-Meier method for survival (OS) and two-paired Fisher exact test or student t test was used for correlations (p<0.05 as significant).
Results: 76 patients (2-85 yrs; Median 49 yrs; Mean 53 yrs; M:F 1:1) with normal cytogenetics were included. FAB subtypes were M0 (6/76, 8%); M1 (14/76, 18%); M2 (16/76, 21%); M4/M5 24/76, 32%); M6/7 (6/76, 8%); AML with MDS (10/76, 13%). WT1+ was seen among 29(38%) while Wt1-ve staining was noted in 47 (62%) pts. Wt1+ was frequent (52%) among young pts (<60) compared to older pts (>60) (33%) (p <0.05). WT1 positivity among denovo AML (27/66; 41%) compared to AML with MDS related change (2/10; 20%) was insignificant (p=0.301). OS (60 months) among denovo AML WT1+ was 33% compared to 49% among WT1- pts (p 0.027).
Conclusions: Our data outlines that Wt1 protein expression among AML pts with normal cytogenetics is common and is more prominent among younger pts. Wt1 protein as detected by IHC predicts poor overall survival among these pts. Studies to correlate Wt1 protein expression with underlying Wt1 genetic mutations are on going.
Monday, March 19, 2012 2:30 PM
Platform Session: Section C, Monday Afternoon