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.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 158, Tuesday Afternoon