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.

MAL promoter hypermethylation as a novel prognostic marker in gastric cancer

“…This survival benefit was independent of other clinicopathological data such as age, gender, histological type of the tumour, tumour stage and lymph node status. Interestingly, also in Hodgkin's lymphoma patients a similar association was found with a significantly worse survival in patients whose tumours expressed the MAL protein compared with patients with tumours lacking MAL expression (Hsi et al, 2006), indicating a prognostic value of MAL also in other cancer models.…”

Primary mediastinal B‐cell lymphoma

“…12,25,26 Of note, some cases of classical HL (10% to 20%) may also demonstrate MAL expression. 26,27 Among normal B cells, MAL expression is largely restricted to a sub-population of thymic medullary B cells, from which PMBL is believed to arise. No mutations have been identified in MAL, and the mechanism of MAL protein overexpression in PMBL is unclear.…”

Formin INF2 regulates MAL-mediated transport of Lck to the plasma membrane of human T lymphocytes

“…14 Although MAL expression is normally absent from normal B lymphocytes, MAL expression has been found in primary mediastinal B-cell lymphoma 15,16 and in a subset of Hodgkin lymphoma with an adverse outcome. 17,18 Therefore, in addition to the interest of the elucidation of the mechanism of MAL-mediated transport of Lck in normal T cells, the understanding of MAL function in normal cells would be of great help to unveil its role in tumor cells.The mechanism and regulation of MAL-mediated Lck transport in T lymphocytes are addressed in the present paper through the identification of human Inverted Formin2 (INF2) as a binding partner of MAL. INF2 domain organization is similar to that of the diaphanous-related group of formins (Drfs), which are direct effectors of Rho-family guanosine triphosphate (GTP)ases.…”