Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein

Invasive micropapillary carcinoma, a tumor with highly infiltrative characteristics is defined by a distinctive cleft formation around the neoplastic cell clusters which is presumably a result of the detachment of the cells from the stroma due to as yet undetermined factors. Ultrastructural examination performed on a handful of cases demonstrated an unexpected secretory activity in the stroma-facing surface of the cells. MUC1 is a glycoprotein typically expressed in the apical surface of normal epithelial cells, responsible for maintaining lumen formation. In conventional adenocarcinomas, MUC1 expression is largely intracytoplasmic, intercellular, or apical (in glandular areas). The MUC1 expression pattern was investigated by immunohistochemical staining in invasive micropapillary carcinoma of breast (n=11), pancreas (n=5), gynecologic tract (n=11) and urinary bladder (n=10). The results were contrasted with the staining pattern in conventional carcinomas of the same organs (n=202). In all invasive micropapillary carcinoma, MUC1 expression was predominantly in the stroma-facing surface of the cell clusters (basal), accentuating the outlines of the micropapillary units by forming a distinct band on this surface. In conventional carcinoma the labeling was mostly apical in areas with lumen formation and intracytoplasmic and intercellular in the poorly differentiated areas. In conclusion, in the micropapillary pattern of invasive carcinoma, the expression of MUC1, is largely limited to the basal surface of the cells in contrast to conventional carcinomas in which MUC1 is largely apical, intracytoplasmic or intercellular. This provides support for the reversal of cell orientation as an important factor of the morphogenesis and possibly the pathogenesis of invasive micropapillary carcinoma. Since MUC1 is known to have a role in lumen formation, and has an inhibitory role in the cell to stroma interaction, it is conceivable that it is a key factor in the detachment of cells from stroma allowing for the dissection of the connective tissue and easing the spread of cells.