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).
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.
Panelos
John
J
Department of Human Pathology and Oncology, University of Florence, Florence, Italy.
Batistatou
Anna
A
Paglierani
Milena
M
Zioga
Aikaterini
A
Maio
Vincenza
V
Santi
Raffaella
R
Pimpinelli
Nicola
N
De Giorgi
Vincenzo
V
Santucci
Marco
M
Massi
Daniela
D
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*
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D051176:beta Catenin