Lectin and proteoglycan histochemistry of Merkel cell carcinomas

Abstract

Changes in carbohydrate residue expression and in proteoglycan distribution occur during different stages of tumor development and progression. However, few data concerning carbohydrate residue analysis as performed by lectin histochemistry and proteoglycan distribution of Merkel cell carcinoma, a rare malignant tumor of the skin, have been reported. Hence, lectin- and proteoglycan immunohistochemistry was performed on paraffin wax material of 9 cases of Merkel cell carcinomas characterized by cytokeratin and neurofilament 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 using Con A (mannose/glucose-specific) followed by LCA with the same specificity and the N-Acetyl glucosamine-specific lectins (WGA, UDA, CMA), while no fucose binding sites were detected (UEA-I). In addition, N-Acetyl galactosamine residues were only occasionally detected. The lectin binding pattern of Merkel cell carcinoma cells indicated that predominantly N-linked glycans and not O-linked glycans, typical for mucins of most epithelia, were present. Hence these tumor cells were relatively undifferentiated and resembled stem cells more closely than differentiated epithelia. The tumor stroma was especially evaluated in this study and showed a lectin reaction, which was intermediate between the tumor cells and extra-tumoral stroma. For example, 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 reaction. These results indicated an influence of tumor cells on the stromal constituents. Antibodies against chondroitin type glycosaminoglycans reacted with the tumor stroma and the pericellular substance around the tumor cells most intensely in - and around the major tumor septae which, in general, were well vascularized. The most intensive immunoreactivity was detected using the chondroitin-6-sulfate antibody. The cellular and membrane-associated reaction for heparan sulfate was less intensive in comparison to epidermal cells. In conclusion the pattern of lectin-binding sites, the high chondroitin(sulfate) specific reactivity and the relatively low intensity of heparan sulfate immunohistochemistry indicate a low degree of differentiation and high malignity of the tumors, which is consistent with the clinical behavior of Merkel cell carcinomas.

What can primary cutaneous neuroendocrine carcinomas with squamoid and neuroendocrine differentiation teach us about the origin of Merkel cells?

“…20 A third and increasingly popular hypothesis is that MCCs originate from epidermal stem cells, with the capacity to differentiate into both neuroendocrine and epidermoid lineages. 22 This hypothesis may explain case reports of intraepidermal MCCs (MCC in situ), MCCs showing squamous metaplasia, and mixed MCCs and squamous cell carcinomas. 23,24 In our department, we have recently seen a primary cutaneous neuroendocrine carcinoma that showed this dual differentiation (Fig.…”

Lectins as Bioactive Plant Proteins: A Potential in Cancer Treatment

“…The lectin-binding pattern of tumor cells varies among lectins with different sugar-binding specificities, while it is remarkably similar among tumors within a given nominal sugar specificity. Sames et al (2001) studied the reactions of Merkel cell skin carcinomas to lectins and observed that the most intense reaction was achieved using Con A (mannose/glucose-specific), followed by LCA with the same specificity, and the N -acetylglucosamine-specific lectins (WGA, UDA, CMA), while no fucose-binding sites were detected (UEA-I). In addition, galNAc residues were only occasionally detected.…”

Pea, Pisum sativum, and its anticancer activity

“…[56] Other legume lectins also have antiproliferative and anticancer properties such as concanavalin A, a lectin from Jack bean seed. [57] Several studies have suggested the cytotoxicity or tumor inhibition mechanisms of lectins to various tumor cell lines such as skin,[58] liver, bile duct, and bone cell lines. [59]…”