Paget's disease (PD) of the skin is characterized by intraepidermal
adenocarcinoma cells, which contain clear cytoplasm and abundant
mucin. Nearly all cases of mammary PD (MPD) are associated with underlying
ductal carcinoma of the breast, whereas in the majority of cases of extramammary PD (EMPD) no underlying regional
malignancy is identified.
Mucins are high molecular weight
glycoproteins produced by epithelial cells. Different
mucin genes are expressed in various types of tissues such as mammary glands, intestinal mucosa, and adnexal structures of the skin. We studied the immunohistochemical expression of
apomucin MUC1, MUC2, MUC5AC in MPD, and EMPD. MUC1 is commonly expressed in most cases of PD. MUC5AC is a unique
mucin that is exhibited in the majority of cases of EMPD, but not in any MPD. Of the 13 patients with MPD who all had associated
breast ductal carcinoma, both Paget cells 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 MPD. Of the three patients with perianal PD who all had associated rectal
adenocarcinoma, Paget's cells expressed MUC2 constantly but expressed MUC1 and MUC5AC variably. Seven patients with intraepidermal vulvar PD and two patients with scrotal-penile PD had no identifiable underlying
malignancy. Paget 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 underlying apocrine
carcinoma had a phenotype (MUC1+MUC2-MUC5AC-) identical to that of normal apocrine glands. The skin appendage and Bartholin's glands from 20 normal-appearing vulvar skin samples and anal glands from 10
hemorrhoidectomies were also studied. Only Bartholin's gland expressed a
mucin phenotype identical to that of intraepidermal EMPD. The results of the present study 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 unidentified glands, and 3) unique expression of MUC2 in perianal PD indicates its origin from colorectal mucosa. We conclude that the study of
mucin gene expression is useful in identifying the histogenesis of PD.