Histochemistry of glycoconjugates in Merkel cell carcinomas

Glycoproteins and proteoglycans are involved in tumor genesis, progression, and metastatic activity. Hence, glycoprotein and proteoglycan immunohistochemistry was applied to material of nine cases of Merkel cell carcinomas preserved in paraffin. Merkel cell tumors were identified by cytokeratin and neurofilament immunohistochemistry. Antibodies against laminin and type IV collagen were used to reveal basement membrane material. An atypical distribution of laminin and type IV collagen with localization outside the basement membranes suggests high invasiveness. The reduced intensity of the cellular and cell membrane-associated reaction of heparan sulfate (HS) antibodies in comparison to normal epidermal cells may be a sign of low differentiation. The intensive reaction of antibodies against chondroitin (Ch)-type glycosaminoglycans with the tumor stroma and the pericellular substance in-and-around well-vascularized tumor septae may indicate high proliferation and migration activity of the cells. O-Linked glycans, typical for the mucins of most epithelia seem to be absent as shown by the lectin binding pattern of Merkel cell carcinoma cells, a fact underlining the undifferentiated state of the tumor cells. Mannose-specific lectins not applied before to Merkel cell tumors as well as HPA showed no reaction or only weak reactions with the tumor cells. The lectin reaction of the tumor stroma, was intermediate between the tumor cells and extra-tumoral stroma indicating an influence of tumor cells on the stromal constituents in the Merkel cell carcinoma. The findings point to a low degree of differentiation and high malignancy of the tumors. The methods used have proved to be of diagnostic and prognostic value and should be further standardized for such purposes.