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) (Journal article)

Panelos, J./ Batistatou, A./ Paglierani, M./ Zioga, A./ Maio, V./ Santi, R./ Pimpinelli, N./ De Giorgi, V./ Santucci, M./ Massi, D.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adult,Aged,Aged, 80 and over,Cadherins/*metabolism,Carcinoid Tumor/metabolism/pathology,Carcinoma, Merkel Cell/*metabolism/mortality/secondary,Cell Adhesion,Cell Membrane/metabolism/pathology,Cytoplasm/metabolism/pathology,Down-Regulation,Female,Fluorescent Antibody Technique, Indirect,Humans,Immunoenzyme Techniques,Male,Middle Aged,Receptor, Notch1/*metabolism,Skin Neoplasms/*metabolism/mortality/pathology,Survival Rate,Tumor Markers, Biological/metabolism,beta Catenin/*metabolism
ISSN: 1530-0285
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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