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

Abstract

Aims: To investigate whether MUC1 mucin, a high molecular weight transmembrane glycoprotein, also known as epithelial membrane antigen (EMA), differs in its expression and degree of glycosylation between anaplastic large cell lymphoma (ALCL) and classic Hodgkin's disease (HD), and whether MUC1 immunostaining can be used to differentiate between CD30 positive large cell lymphomas.

Methods/results: Using five different monoclonal antibodies (E29/anti-EMA, DF3, 139H2, VU-4H5, and SM3) that distinguish between various MUC1 glycoforms, high MUC1 expression (50-95% of tumour cells positive) was found in 13 of 17 anaplastic lymphoma kinase (ALK) positive systemic nodal ALCLs, and in one of 20 cases of classic HD. Scattered or focal staining (< 25% of tumour cells) was seen in two additional ALK positive systemic ALCLs, two additional classic HD cases, and in three of 20 cases of ALK negative systemic nodal ALCL. Primary cutaneous ALCL showed no staining with the anti-MUC1 antibodies. Antibodies detecting hypoglycosylated MUC1 were found to be absent in all lymphomas (SM3) or present in only six of 15 ALK positive ALCLs (VU-4H5).

Conclusions: MUC1 is preferentially expressed by a subtype of systemic nodal ALCL, characterised by ALK expression, but is found in only a few cases of classic HD and ALK negative ALCL. Therefore, although MUC1 could be used in a panel of markers for CD30 positive lymphomas, it is probably not a valuable tool to differentiate between ALK negative CD30 positive large cell lymphomas. Finally, the degree of MUC1 glycosylation in lymphomas is relatively high, compared with the aberrant hypoglycosylation found in adenocarcinomas.

Figure 1 Extended MUC1 mucin molecule on a cell surface membrane with O-linked and N-linked glycosylated side chains. The insert shows a MUC1 20 mer single repeat peptide with O-linked hypoglycosylated side chains.

Figure 2 (A) ALK positive systemic nodal anaplastic large cell lymphoma (ALCL) case, showing membranous MUC1 expression in most of the tumour cells with the monoclonal antibody E29 (anti-EMA). (B) Another ALK positive systemic nodal ALCL case, showing both membranous, cytoplasmic, and occasional dot-like staining of the Golgi area of tumour cells with monoclonal antibody E29. (C) ALK negative systemic nodal ALCL case, showing tumour cells negative for antibody DF3, whereas plasma cells are positive, serving as an internal positive control. (D) ALK positive systemic nodal ALCL case, showing cytoplasmic and sometimes membranous staining with the VU-4H5 antibody. (E) Nodular sclerosing case of classic Hodgkin's disease, showing DF3 staining in a typical Reed-Sternberg tumour cell.