Normal respiratory mucosa, precursor lesions and lung carcinomas: Differential expression of human mucin genes

Mucins are glycoproteins synthesized by epithelial cells and thought to pro mote tumor-cell invasion. Eight human mucin genes have been well characteri zed: MUC2, MUC5AC, MUC5B, MUC6 map to 11p15.5 and encode secretory gel form ing mucins while MUC1, MUC3, MUC4, MUC7 are scattered on different chromoso mes and encode membrane-bound or secreted mucins. The expression pattern of the mucin genes is complex in normal airways involving six genes, mainly M UC5AC and MUC5B in mucus-producing cells and MUC4 in a wide array of epithe lial cells. MUC5AC overexpression in metaplasia, dysplasia and normal epith elium adjacent to squamous cell carcinoma provides additional arguments for a mucous cell origin of preneoplastic squamous lesions. MUC5AC and MUC5B e xpression is related to mucus formation in adenocarcinomas. Mucinous bronch ioloalveolar carcinoma (BAC) has a particular pattern of mucin gene express ion indicating that it has sustained a well-differentiated phenotype simila r to the goblet cell, correlated with distinctive features i.e. a noninvasi ve pattern and a better prognosis than nonBACs. MUC4 is the earlier mucin g ene expressed in the foregut, before epithelial differentiation and is expr essed independently of mucus secretion both in normal adult airways and car cinomas. These findings are in favor the histogenetic theory of non-small-c ell carcinoma originating from a pluripotent mucous cell.