MAL Is Expressed in a Subset of Hodgkin Lymphoma and Identifies a Population of Patients With Poor Prognosis

Abstract

Classical Hodgkin lymphoma (cHL) and mediastinal (thymic) large B-cell lymphoma (MLBL) have clinical, histopathologic, and molecular genetic similarities. MAL, a gene that encodes a protein associated with lipid rafts in T and epithelial cells, is overexpressed in a majority of MLBLs and has been reported in a minority of cHLs. To study the clinical significance of MAL in cHL, we immunostained 86 cases; 16 cHLs (19%) expressed MAL. Expression correlated with nodular sclerosis subtype, and within this subtype, with grade 2 histology. Univariable analysis revealed association of age of 45 years or older, MAL expression, and an International Prognostic Score of more than 2 with worse failure-free survival. Age of 45 years or older, MAL expression, and stage III or IV were associated with worse overall survival (OS). Cox proportional hazards modeling showed age (P = .04 and P = .03, respectively) and MAL expression (P = .03 and P = .01, respectively) as independent predictors of time to failure-free survival and OS. Stage showed borderline significance in OS (P = .08). MAL expression seems to identify a subset of cHL with an adverse outcome and provides additional evidence for a link between cHL and MLBL.

Inactivation of the MAL Gene in Breast Cancer Is a Common Event That Predicts Benefit from Adjuvant Chemotherapy

“…In esophageal cancer, MAL was suggested to be a tumor suppressor gene based on studies showing that MAL expression repressed the formation of tumors induced by TE3 cells in nude mice, inhibited cell motility, and induced apoptosis via the Fas signaling pathway (18). Furthermore, MAL expression was indicative of disease outcome and prognosis for patients with T cell lymphoma (26), Hodgkin lymphoma (27), and serous ovarian cancer (15). The function of MAL in normal or neoplastic breast epithelial cells is unknown, however its location in the detergent insoluble fraction in HCC1937 cells suggests that similar to other cell types, it plays an integral role in membrane microdomains.…”

BOB.1, CD79a and cyclin E are the most appropriate markers to discriminate classical Hodgkin’s lymphoma from primary mediastinal large B‐cell lymphoma

“…Markers used in daily diagnostic practice and experience from our previous studies 16,19 as well as the data of other investigators, addressing marker expression in cHL and PMBCL, were taken into consideration 11 . Markers with poor reproducibility (Bcl‐6 and CD45RA) as well as markers reported to be expressed in substantial proportions of cases of both entities (c‐Rel and MAL) 20–23 were not considered.…”

Hodgkin Lymphoma: An Update on its Biology with New Insights into Classification

“…Both NSCHL and PMLBL lack immunoglobulin expression and functional expression of HLA class I antigens, and share cytogenetic abnormalities. MAL , a gene involved in T-cell activation that is expressed in PMLBL, is only expressed by NSCHL and no other HL subtypes 12. CD23, which is expressed on normal thymic B-cells and PMLBL, is also expressed in some cases of NSCHL.…”