Lectin and proteoglycan histochemistry of Merkel cell carcinomas

Changes in carbohydrate residue expression and in proteoglycan distribution occur during different stages of tumor development and progression. Howeve r, few data concerning carbohydrate residue analysis as performed by lectin histochemistry and proteoglycan distribution of Merkel cell carcinoma, a r are malignant tumor of the skin, have been reported. Hence, lectin- and pro teoglycan immunohistochemistry was performed on paraffin wax material of 9 cases of Merkel cell carcinomas characterized by cytokeratin and neurofilam ent immunohistochemistry. The lectin binding pattern of tumor cells varied between lectins with different sugar binding specificities, while within a given nominal sugar specificity intensities were remarkably similar between tumors from different patients. The most intensive reaction was observed u sing Con A (mannose/glucose-specific) followed by LCA with the same specifi city and the N-Acetyl glucosamine-specific lectins (WGA, UDA, CMA), while n o fucose binding sites were detected (UEA-I). In addition, N-Acetyl galacto samine residues were only occasionally detected. The lectin binding pattern of Merkel cell carcinoma cells indicated that predominantly N-linked glyca ns and not O-linked glycans, typical for mucins of most epithelia, were pre sent. Hence these tumor cells were relatively undifferentiated and resemble d stem cells more closely than differentiated epithelia. The tumor stroma w as especially evaluated in this study and showed a lectin reaction, which w as intermediate between the tumor cells and extra-tumoral stroma. For examp le, the reactions of N-Acetyl galactosamine-specific lectins were intensive in the extra-tumoral stroma but nearly negative in tumor cells, while the lectin reaction of the intra-tumoral stroma was similar to the cellular rea ction. These results indicated an influence of tumor cells on the stromal c onstituents. Antibodies against chondroitin type glycosaminoglycans reacted with the tumor stroma and the pericellular substance around the tumor cell s most intensely in - and around the major tumor septae which, in general, were well vascularized. The most intensive immunoreactivity was detected us ing the chondroitin-6-sulfate antibody. The cellular and membrane-associate d reaction for heparan sulfate was less intensive in comparison to epiderma l cells. In conclusion the pattern of lectin-binding sites, the high chondr oitin(sulfate) specific reactivity and the relatively low intensity of hepa ran sulfate immunohistochemistry indicate a low degree of differentiation a nd high malignity of the tumors, which is consistent with the clinical beha vior of Merkel cell carcinomas.