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


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.
ten Berge
R L
RL
Department of Pathology, University Hospital Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. rl.tenberge@azvu.nl
Snijdewint
F G
FG
von Mensdorff-Pouilly
S
S
Poort-Keesom
R J
RJ
Oudejans
J J
JJ
Meijer
J W
JW
Willemze
R
R
Hilgers
J
J
Meijer
C J
CJ
D000077548:Anaplastic Lymphoma Kinase; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D003937:Diagnosis, Differential; D006031:Glycosylation; D006689:Hodgkin Disease / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000737:chemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry* / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000737:chemistry; D018396:Mucin-1 / Q000032:analysis* / Q000276:immunology; D020033:Protein Isoforms / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D018396:Mucin-1; D020033:Protein Isoforms; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate