Differential expression of mucin genes in mammary and extramammary Paget'sdisease

Paget's disease (PD) of the skin is characterized by intraepidermal adenoca rcinoma cells, which contain clear cytoplasm and abundant mucin. Nearly all cases of mammary PD (MPD) arc associated with underlying ductal carcinoma of the breast, whereas in the majority of cases of extramammary PD (EMPD) n o underlying regional malignancy is identified. Mucins are high molecular w eight glycoproteins produced by epithelial cells. Different mucin genes are expressed in various types of tissues such as mammary glands, intestinal m ucosa, and adnexal structures of the skin. We studied the immunohistochemic al expression of apomucin MUC1, MUC2, MUC5AC in MPD, and EMPD. MUC1 is comm only expressed in most cases of PD. MUC5AC is a unique mucin that is exhibi ted in the majority of cases of EMPD, but, not in any MPD. Of the 13 patien ts with MPD who all had associated breast ductal carcinoma, both Paget cell s and underlying ductal carcinoma exhibited the phenotype (MUC1+MUC2-MUC5AC -), This mucin phenotype is also expressed by Toker cells, which have been identified in the epidermis of five of 50 nipples in mastectomies without M PD. Of the three patients with perianal PD who all had associated rectal ad enocarcinoma, Paget's cells expressed MUC2 constantly but expressed MUC1 an d MUC5AC variably. Seven patients with intraepidermal vulvar PD and two pat ients with scrotal-penile PD had no identifiable underlying malignancy. Pag et cells from all of these nine cases of EMPD expressed a uniform phenotype of mucin (MUC1+MUC2-MUC5AC+). One case of vulvar PD associated with underl ying apocrine carcinoma had a phenotype (MUC1+MUC2-MUC5AC-) identical to th at of normal apocrine glands. The skin appendage and Bartholin's glands fro m 20 normal-appearing vulvar skin samples and anal glands from 10 hemorrhoi dectomies were also studied. Only Bartholin's gland expressed a mucin pheno type identical to that of intraepidermal EMPD. The results of the present s tudy indicate that 1) MPD may arise from either mammary glands or epidermal Toker cells, 2) intraepidermal EMPD in the anogenital areas may arise from ectopic MUC5AC+ cells originating from Bartholin's or some other unidentif ied glands, and 3) unique expression of MUC2 in perianal PD indicates its o rigin from colorectal mucosa. We conclude that the study of mucin gene expr ession is useful in identifying the histogenesis of PD.