B-Lymphoblastic Leukemia/Lymphoma (B-ALL) with Favorable Cytogenetics: Expression of PAX5 Defines a Subgroup with Poor Overall Survival
Payam Pournazari, Aleena Mansoor, Farid Kosari, Xiu Jiang, Iwona Auer, Thomas Fourie, Jay Patel, Victor Lewis, Doug Demetrick, Douglas Stewart, Meer-Taher Shabani-Rad. University of Calgary/Calgary Laboratory Services (CLS), Calgary, AB, Canada; University of Calgary, Calgary, AB, Canada
Background: Recurrent genetic abnormalities defines risk stratification among B-ALL (WHO-2008). t(9;22), Hypodipolidy and MLL gene rearrangements are considered poor prognostic while, normal karyotype, hyperdiploidy and t(12;21) are believed to have favorable prognosis. Gene expression profile data has recently identified various genes to be associated with pathogenesis and prognosis, specially among patients with normal cytogenetics. PAX5 is a key player in B-cell differentiation and development. We have studies the expression of PAX5 protein by IHC in a homogenous population of B-ALL patients (pts) and correlated its expression with cytogenetic and clinical outcome data.
Design: Pts were diagnosed according to WHO 2008 criteria. Diagnostic BM biopsy samples (FFPE) were used (triplicate, 0.6 mm) to create TMAs. Standardized IHC staining protocol, utilizing automatic immunostainer (Ventana, Tucson, AZ) was used for PAX5 staining (1:10; clone G148-74, Pharmingen, San diego, CA). Staining intensity was scored on 4-tier system without the knowledge of the clinical outcome. All pts received standardized chemotherapy +/- BMT. SPSS software was utilized for overall survival (OS) (Kaplan-Meier) and correlation (two tail fisher exact t test).
Results: 130 pts (1-82 yrs; median 11 yrs; mean 23.7 yrs; M:F 1.1:1) were included. Differential expression of PAX5; 0 (20/15%); 1(15/11%); 2(24/19%); 3 (40/ 31%); 4(31/24%) was noted. Strong correlation was noted between PAX5 expression and age <15 (p<0.004; r 0.318) compared to adult ALL (age >30 yrs; p< 0.089). Poor prognosis cytogenetic was noted among 58 (45%) while favorable cytogenetics was noted among 72 (55%) pts. Higher expression of PAX5 (≥3) correlated with shorter OS (p=0.002) (at 60 m f/u) among good prognostic group, vs. poor prognosis group (p = 0.987).
Conclusions: Our results show that there is a differential pattern of PAX5 protein expression in B-ALL. PAX5 protein positivity is mostly seen in pediatric age group. PAX5 is associated with shorter OS among patients with cytogenetic abnormalities associated with favorable prognostic.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 237, Wednesday Afternoon