[1272] 1p36 Microdeletions Are Prevalent among B-Cell Non-Hodgkin Lymphomas and Associated with PAX7 Loss.

Alejandro A Gru, Friederike Kreisel, Mohammad Hussaini, Tu-Dung Nguyen, John L Frater, Anjum Hassan. Washington University in St. Louis School of Medicine, MO

Background: Deletion of the 1p36 locus (1p36mdel) has been proposed as a defining genetic aberration in a subset of low-grade follicular lymphomas (FL) with diffuse morphology (DFL). DFL appear to have a relative better prognosis compared to FL with nodular morphology. However, the prevalence and prognostic significance of 1p36mdel has not been adequately studied in other B-cell Non-Hodgkin Lymphomas (BNHLs). Tumor suppressor genes, such as PAX7 and CDC2L1, are mapped in this region.
Design: 112 cases of BNHLs were retrieved between 1998 -2009: 13 cases of low-grade FL, 7 cases of low-grade DFL, 5 cases of FL vs marginal zone lymphoma (MZL), 2 of grade 3 FL, 12 cases of MZL, 28 cases of mantle cell lymphoma (MCL), 11 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), 30 cases of diffuse large B cell lymphoma (DLBCL), 1 case of lymphoplasmacytic lymphoma (LPL), and 4 cases of unclassifiable B NHL. The diagnosis was reviewed by 2 different hematopathologists. Demographics, Ann Arbor stage, treatment, survival (in months), time to recurrence, and molecular/ cytogenetics studies was recorded, when available. Interphase fluorescent in-situ hybridization (FISH) was performed on formalin-fixed paraffin embedded tissue using a novel probe for 1p36mdel and 1q42 (Vysis). Immunohistochemistry for PAX7, CDC2L1 and TNFR1 was performed using a Ventana autostainer. Statistical analysis, using SPSS V13.0, was done for student t-test, Kaplan-Meier and Cox-Wilson regression.
Results: Overall, FISH detected 1p36mdel in 86% of DFL (6/7), 40% of FL vs MZL (2/5), 42% of MZL (5/12), 46% of low-grade FL (6/13), 26% of DLBCL (8/30) and 18% of MCL (5/28). None of the CLLs had 1p36mdel (0/11). Conventional cytogenetics, performed on 31 cases, showed a 1p deletion in a single case (3%). The prevalence of 1p36mdel in BNHL was estimated as 29%. The sensitivity and specificity of the probe for the diagnosis of DFL was 86% and 8.3%, respectively. The presence of 1p36mdel had significant correlation with a better survival and time to recurrence of disease in the FL group compared to the negative group (mean 73.5 vs 17.18 months, p=0.009). No differences in survival were noted in MZL, MCL, or DLBCL. 1p36mdel was associated with PAX7 loss by IHC (68% vs 45%, p=0.025) and no significant difference in CDC2L1 (44% vs 35%, p=0.11).
Conclusions: 1p36 mdel is a frequent event across different subtypes of NHL, and not specific for DFL. It is associated with overall better survival in FL, and loss of PAX7 expression by IHC.
Category: Hematopathology

Tuesday, March 1, 2011 1:00 PM

Poster Session IV # 158, Tuesday Afternoon

 

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