title: Differential expression of mucins 1-6 in papillary thyroid carcinoma: evidence for transformation-dependent post-translational modifications of MUC1 in situ.
abstract: Mucins are primary glycoproteins of epithelia that are known to undergo major changes in their post-translational processing during neoplastic transformation. This study has examined the expression pattern of seven primary mucins, ie mucin (MUC) 1, 2, 3, 4, 5AC, 5B and 6, in normal, hyperplastic, benign neoplastic, and papillary-type carcinoma (PTC) tissues of the thyroid. MUC1 and MUC5B were the only mucins to be widely transcribed in both benign and malignant tissues. In contrast, MUC4 transcripts were undetectable in normal thyroids, and were present in only 40% of the hyperplastic and malignant thyroid tissues. In PTC, MUC1 was identified as a single mRNA transcript, rejecting the idea that this mucin may undergo transformation-dependent alternative splicing in thyroid tumours. The tissue distribution of MUC1 and MUC4 proteins was highly heterogeneous: this largely paralleled their mRNA expression profiles and supported the conclusion that whereas MUC1 was ubiquitously expressed in PTC, MUC4 was detectable in less than 20% of the cases analysed. In order to determine whether post-translational modifications of MUC1, putatively associated with malignancy, also occurred in the mucin produced by PTC, immunohistochemistry was performed with a panel of well-characterized anti-MUC1 antibodies in conjunction with digestion of the tissue sections with deglycosylating enzymes. These experiments, which were supported by immunochemical analyses of the MUC1 and MUC4 glycoforms extracted from tissues, collectively demonstrated markedly divergent MUC1 glycosylation profiles in normal and benign thyroid tissues when compared with PTC. Characteristically, these latter neoplastic cells produced mucin molecules carrying complex poly-N-lactosamine-type glycans capped with fucose and neuraminic acid residues. The present study also found evidence in PTC for the potential presence of proteolytically processed MUC1 isoforms which differ in their post-translational traits depending on whether they are retained on the cell surface or secreted into the extracellular space. It is proposed that the observed differences in the glycosylation properties of normal and neoplastic MUC1 may be exploitable as an ancillary tool in the diagnosis of PTC.
authors.affiliation: Institute for Anatomic Pathology, University of Catania, Via Biblioteca 4, Catania, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Magro
authors.forename: Monica
authors.initials: M
authors.lastname: Schiappacassi
authors.forename: Daniela
authors.initials: D
authors.lastname: Perissinotto
authors.forename: Antonella
authors.initials: A
authors.lastname: Corsaro
authors.forename: Cinzia
authors.initials: C
authors.lastname: Borghese
authors.forename: Antonino
authors.initials: A
authors.lastname: Belfiore
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Grasso
authors.forename: Carlo
authors.initials: C
authors.lastname: Botti
authors.forename: Emilio
authors.initials: E
authors.lastname: Bombardieri
authors.forename: Roberto
authors.initials: R
authors.lastname: Perris
mesh_terms: D000912:Antibodies, Neoplasm / Q000032:analysis; D002291:Carcinoma, Papillary / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006044:Goiter, Nodular / Q000235:genetics; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D009077:Mucins / Q000032:analysis*; D011233:Precipitin Tests; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D000912:Antibodies, Neoplasm; D009077:Mucins; D012333:RNA, Messenger; D012334:RNA, Neoplasm