title: Expression of Notch-1 and alteration of the E-cadherin/beta-catenin cell adhesion complex are observed in primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma).
abstract: Increasing evidence indicates that Notch signaling contributes to physiological processes, including development and differentiation, as well as tumorigenesis, either as a tumor promoter or suppressor, depending on cellular context, expression levels and cross talk with other signaling systems. Recent studies reported absent or minimal Notch-1 expression in neuroendocrine tumors of the lung and gastrointestinal tract, suggesting a tumor-suppressor function of Notch-1. Merkel cell carcinoma is a rare and highly aggressive primary cutaneous neuroendocrine carcinoma. Because no information is available on Notch-1 expression in this tumor, we have investigated a series of 31 Merkel cell carcinoma for Notch-1 immunoreactivity. Immunoreactivities for E-cadherin and beta-catenin were also analyzed. All but 1 Merkel cell carcinoma (30 of 31) retained cytoplasmic and membrane Notch-1 expression in more than 50% of cells. beta-Catenin displayed a prevalent membrane-associated staining in 30 of 31 cases, and 22 cases showed more than 50% of immunoreactive cells whereas nuclear beta-catenin was seen only in 2 of 31 cases. E-cadherin membranous expression was remarkably low, as only 1 of 26 cases was found positive in more than 50% of cells. In contrast with neuroendocrine tumors in other tissues, evident Notch-1 expression was found in Merkel cell carcinoma. This finding does not support a tumor-suppressor function of Notch-1 in Merkel cell carcinoma. Downregulation of E-cadherin and diffuse membranous beta-catenin expression suggest a dysregulation of the E-cadherin/beta-catenin complex in Merkel cell carcinoma. This may contribute to local invasion and distant metastasis.
authors.affiliation: Department of Human Pathology and Oncology, University of Florence, Florence, Italy.
authors.forename: John
authors.initials: J
authors.lastname: Panelos
authors.forename: Anna
authors.initials: A
authors.lastname: Batistatou
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Zioga
authors.forename: Vincenza
authors.initials: V
authors.lastname: Maio
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santi
authors.forename: Nicola
authors.initials: N
authors.lastname: Pimpinelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Giorgi
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology; D015266:Carcinoma, Merkel Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D051176:beta Catenin