MUC1 (EMA) is preferentially expressed by ALK positive anaplastic large cell lymphoma, in the normally glycosylated or only partly hypoglycosylated form

Abstract

1 In 30-50% of cases, a chromosomal aberration such as the t(2;5)(p23;q35) translocation gives rise to expression of the anaplastic lymphoma kinase (ALK) protein, 2 identifying a subgroup of patients with systemic ALCL with excellent prognosis.3-6 ALK expression seems specific for systemic nodal ALCL; it is not found in classic Hodgkin's disease (HD) 7-11 or primary cutaneous ALCL.7 10 12 13 Morphologically, these lymphomas may closely resemble systemic ALCL, being also characterised by CD30 positive tumour cells with abundant cytoplasm, large irregular nuclei, and a prominent single nucleolus or multiple nucleoli.1 Clinically, however, classic HD and primary cutaneous ALCL have a more favourable prognosis than ALK negative systemic ALCL. 12 14-16 Because of the diVerences in clinical behaviour and subsequent therapeutic strategies, diVerentiating ALK negative systemic ALCL from classic HD or primary cutaneous ALCL is very important.Several markers can be used in the diVerential diagnosis of ALCL and other CD30 positive lymphomas. One such marker is MUC1 mucin, also known as epithelial membrane antigen (EMA).17 18 MUC1 is a high molecular weight transmembrane glycoprotein, usually expressed on the luminal surface of glandular epithelia. [18][19][20] It consists of protein core with a constant cytoplasmic domain of 69 amino acids, and an extracellular domain with a variable number of 20 amino acid tandem repeats, containing serine and threonine residues, to which multiple oligosaccharide side chains are O-linked [21][22][23][24] (fig 1). Since the first rabbit polyclonal antisera raised against human milk fat globule, 17 and the first monoclonal antibodies designated HMFG1 and HMFG2 25 were described, many anti-MUC1 monoclonal antibodies have been generated and characterised. 26 Most react with a dominant epitope within the variable number of tandem repeats of the protein core; namely, the hydrophilic sequence of PDTRPAP. 26-28The specificity of antibody binding to the protein core depends largely on the extent of MUC1 glycosylation; during the ISOBM TD-4 workshop, clusters of monoclonal antibodies were identified that distinguish between the various glycoforms of MUC1. 29 30 Although MUC1 is defined as an epithelial antigen, in 1984 Delsol et al reported that lymphoid cells and malignancies express EMA. 31Since then, EMA (or more appropriately, MUC1) has been found to be consistently J Clin Pathol 2001;54:933-939 933

Characterization of MUC1 glycoprotein on prostate cancer for selection of targeting molecules

“…Expression of MUC1 epitopes with reduced branching of O-glycans has been observed in breast cancer tissue (18,21) and was reflected by increased staining with MAbs recognizing hypoglycosylated MUC1 (17,20,(22)(23)(24)(25)(26)(27). However, not all cancers express high levels of hypoglycosylated MUC1 epitopes and cancer progression is not always associated with this MUC1 form (11,28,29).…”

Galectin-3 Expression in Primary Cutaneous CD30-Positive Lymphoproliferative Disorders and Transformed Mycosis Fungoides

“…Because of its unique structure, Gal-3 is able to interact with a broad spectrum of ligands. One of its natural ligands is the EMA [14]. EMA is preferentially expressed in ALK-1+ nodal ALCL; PCALCL are EMA- in most cases [15,16], as found in the test cases of this study.…”

“…In all of these cases ALK (anaplastic lymphoma kinase) was negative. LYP cases were histologically subclassified as type A (36), type B (1) and type C (8) as described [1,2,13,14]. In 2 cases a mixed type of A and C was found.…”

Recent Progress and New Perspectives in Lymphoma Glycobiology

“…The data suggested that galectin -3 plays an important role in cell -to -cell interactions. Furthermore, the epithelial membrane protein (EMA), which is one of the galectin -3 ligands, was expressed in many ALCL cell lines including the Karpas 299 cell line (in our preliminary data) and in some cases of ALCL 77) . Taken together with these data there is a possibility that galectin -3 may act as a cell adhesion molecule in the interactions between galectin -3 and EMA.…”