Differential Expression of Pax-5 Protein among B Lymphoblastic Leukemia/Lymphoma (B-ALL) with Recurrent Genetic Abnormalities. Clinical Significance and Association with Hyperdiploidy.
Aleena Masoor, Imran Mirza, Meer Shahbani Taher-Rad, Zohre Mohammad-Taheri, Emina E Torlakovic. University of Calgary, AB, Canada; University of Alberta, Edmonton, Canada; UHN, University of Toronto, ON, Canada
Background: Stratification of B-ALL is based on recurrent genetic abnormalities (WHO 2008) in relation with clinical outcome. GEP data suggest that genetic aberrations in early B-cell development play a significant role in pathogenesis and biological course in B-ALL. Pax5 is critical to B-cell development at pro-B cell stage. Among B-ALL pts, deletions of genes involved in B-cell development (including PAX5) have recently been associated with aggressive disease (Lancet Oncology 2009). In a homogenous cohort of B-ALL pts, expression of PAX5 by IHC was correlated with immunophenotype, cytogenetic and clinical outcome data.
Design: Pts were classified as B-ALL, utilizing morphology, flow-cytometry and cytogenetic data (WHO 2008). FFPE BM biopsy tissue was used to create tissue microarray (TMA). IHC staining was performed using PAX5 Ab (Dako) after heat-induced antigen retrieval, utilizing automated immunostainer (Ventana, Tucson, AZ). Nuclear staining pattern was scored among blast cells on a 4- tier system (<25%;25-50%; 26-75% &>75%) without knowledge of clinical outcome. Correlation of PAX5 expression with cytogenetic data was possible in limited subgroups (normal vs. hyperdiploidy). All pts received standardized chemotherapy +/- BMT. Follow-up (FU) data was collected by chart review. Kapplan-Meier survival plots, Log Rank and Cox regression for overall survival (OS), Linear-by-Linear test and Spearman's correlation were used for analyses.
Results: 88 pts (1-73 yrs; median 11 yrs; M:F 1.4:1) were included. 22/88 (25%) were negative for PAX5 while others show differential expression; <25% (12/88, 14%); 26-50% (19/88,22%); 51-75% (21/88, 24%) and >75% positive blasts (14/88, 16%). Positive correlation was noted with age at diagnosis (p=0.0004, r=0.318); CD34 expression (p=0.04), CD10 expression (p=0.04;). Pax5 expression (>1+) was associated with significantly shorter OS (p=0.019) (OS 65% vs. 95% at 90 months follow up). PAX5 was significantly reduced among hyperdiploidy group (p=0.015, Mann-Whitney U Test) compared to subgroup with normal karyotype.
Conclusions: Our results show that PAX5 protein expression as detected by IHC is associated with shorter OS among B- ALL pts and is significantly reduced among pts with hyperdiploidy.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 154, Wednesday Morning