[1523] Expression of the Anti-Oxidative Protein Paraoxonase 2 (PON2) in Malignant Lymphoma

Aaron M Udager, Delphine Rolland, Farah Keyoumarsi, Dafydd G Thomas, Kojo SJ Elenitoba-Johnson, Megan S Lim, Nathanael G Bailey. University of Michigan, Ann Arbor, MI

Background: Paraoxonase 2 (PON2) is an intracellular, membrane-bound aromatic esterase with anti-oxidative functions. Expression of PON2 contributes to tumorigenesis by inhibiting oxidative stress-induced apoptosis. Through glycoprotein-enriched mass spectrometry-based proteomic profiling, we found that PON2 was highly expressed in mantle cell lymphoma (MCL), anaplastic large cell lymphoma (ALCL), and classical Hodgkin lymphoma (cHL). Overexpression of PON2 has been described in human malignancies, but its expression in lymphoma has not been reported. In this study, we evaluated the expression of PON2 in a large cohort of lymphomas.
Design: A monoclonal anti-PON2 antibody (clone AF3E6, Abcam, Cambridge, MA) was used to assess PON2 expression in lymphomas by western blotting and immunohistochemistry (IHC). Lymphoma cell lines derived from MCL, Burkitt lymphoma (BL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), cHL, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), primary mediastinal large B-cell lymphoma (PMBL), and ALCL were selected for western blot analysis. IHC for PON2 was performed on tissue microarrays of cHL, DLBCL, MCL, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), BL, FL, and ALCL (ALK+ and ALK-). Tissues were scored as positive for PON2 if more than 25% of the neoplastic cells exhibited strong staining. Z-test for independent proportions was used for statistical analysis.
Results: Western blotting showed overexpression of PON2 in MCL and ALK+ ALCL cell lines, as well as a subset of cHL and DLBCL cell lines, while BL, FL, NLPHL, and PMBL cell lines lacked significant PON2 expression. PON2 was strongly expressed in all clinical samples of ALCL, ALK+; most cHL and MCL; and in a subset of CLL/SLL, DLBCL, FL, and ALCL, ALK-. No BL cases exhibited expression.

Frequency of PON2 Overexpression
cHL56/68 (82.4%)
DLBCL30/107 (28.0%)
MCL20/30 (66.7%)
CLL/SLL34/74 (45.9%)
BL0/18 (0%)
ALCL, ALK+5/5 (100%)
ALCL, ALK-4/9 (44.4%)
FL24/91 (26.4%)

Conclusions: PON2 exhibited differential expression in human lymphomas. PON2 was expressed in a higher proportion of ALK+ ALCL compared to ALK- ALCL (100% v. 44.4%, Z=2.079, p=0.04) and was expressed in all ALK+ ALCL cell lines. PON2 was more frequently expressed in non-germinal center (GC) B-cell lymphomas (MCL and CLL/SLL) than in GC B-cell lymphomas (FL and BL) (51.9% v. 22.0%, Z=4.528, p<0.001). Up-regulation of PON2 may be biologically important in a subset of lymphomas as it appears to protect against oxidative stress, and PON2 may be a potential therapeutic target in some lymphoma subtypes.
Category: Hematopathology

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 271, Tuesday Afternoon


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