This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Doglioni, C. Articles by Maestro, R. Search for Related Content PubMed PubMed Citation Articles by Doglioni, C. Articles by Maestro, R.

(American Journal of Pathology. 2003;163:2277-2287.)
© 2003 American Society for Investigative Pathology

Alterations of ß-Catenin Pathway in Non-Melanoma Skin Tumors

Loss of -ABC Nuclear Reactivity Correlates with the Presence of ß-Catenin Gene Mutation

Claudio Doglioni^*, Sara Piccinin, Silvia Demontis, Maria Giulia Cangi^*, Lorenza Pecciarini^*, Concetta Chiarelli^*, Michela Armellin, Tamara Vukosavljevic, Mauro Boiocchi and Roberta Maestro

From the Department of Histopathology,^* Belluno City Hospital, Belluno; and the Department of Experimental Oncology, CRO IRCCS, Aviano National Cancer Institute, Aviano, Italy

To determine the role of ß-catenin pathway in human skin carcinogenesis, 135 non-melanoma skin tumors were analyzed for ß-catenin expression and gene mutations. Intense nucleo-cytoplasmic immunoreactivity for C terminus ß-catenin antibodies was observed in all pilomatricomas and in single cases of trichoepithelioma and squamous cell carcinoma showing peculiar signs of matrical differentiation. Moderate increase of ß-catenin nuclear staining was detected in a significant proportion of basal cell carcinomas, Bowen disease, spiroadenomas, and occasionally also in squamous cell carcinomas, but in these neoplasms only a limited fraction of tumor cells accumulated ß-catenin. Molecular analysis revealed that ß-catenin gene mutations are a peculiar feature of skin tumors with matrical differentiation and correlate with a pattern of intense and diffuse ß-catenin nuclear expression. In contrast, adenomatous polyposis coli (APC) and AXIN2 mutations were not involved in skin tumorigenesis. Analysis of Wnt pathway revealed that TCF-1 and MITF-M were selectively induced in the tumor types harboring ß-catenin mutations, indicating that a Wnt/ß-catenin pathway involving TCF-1 and MITF-M is activated in these tumors. Interestingly, high expression levels of TCF-3 were found in basal cell carcinomas and spiroadenomas. TCF-3 is reported to act as a negative modulator of ß-catenin degradation pathway. Thus, the moderate increase of ß-catenin nuclear staining detected in these tumor types might, at least in part, be due to a TCF-3-dependent mechanism. Finally, we found that the presence of ß-catenin mutations significantly correlated with loss of nuclear immunoreactivity for an antibody raised against the N terminus of ß-catenin (ABC). Thus, a combined analysis with C terminus-ß-catenin antibodies and ABC Ab may represent a powerful investigative approach for the detection of ß-catenin structural alterations.

This article has been cited by other articles:

				S. Pizzi, C. Azzoni, E. Tamburini, L. Bottarelli, N. Campanini, T. D'Adda, G. Fellegara, T. V. Luong, C. Pasquali, G. Rossi, et al. Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of {beta}-catenin and chromosomal instability Endocr. Relat. Cancer, December 1, 2008; 15(4): 1013 - 1024. [Abstract] [Full Text] [PDF]

				J. L. Burchette, T. T. Pham, S. P. Higgins, J. L. Cook, and A. P. Soler Expression of Cadherin/Catenin Cell--Cell Adhesion Molecules in a Onychomatricoma International Journal of Surgical Pathology, July 1, 2008; 16(3): 349 - 353. [Abstract] [PDF]