WNT-1 expression in basal cell carcinoma of head and neck. An immunohistochemical and confocal study with regard to the intracellular distribution of beta-catenin.
BACKGROUND
The WNT gene family is a group of developmental genes involved in cell growth regulation, differentiation and organogenesis in both vertebrates and invertebrates. These genes are also involved in oncogenesis: beta-catenin, a component of the WNT pathway, has been reported to be involved in the genesis of numerous human cancers. WNT-1 pathway signaling is mediated via interactions between beta-catenin, a multifunctional protein playing an important role in cell-to-cell adhesion and gene expression, and members of the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta-catenin protein and determines its accumulation in the cytoplasm and nucleus.


METHODS
In order to evaluate the role of WNT-1 in the neoplastic progression of basal cell carcinoma (BCC), an immunohistochemical and confocal study of its expression and its correlation with beta-catenin distribution was performed in 46 selected cases of BCCs of the head and neck region.


RESULTS
While normal skin showed a WNT-1-positive staining only of the cutaneous annexa and a few cells in the basal/parabasal layers, the areas of de-differentiated BCCs showed a high granular positive staining (50-80% of cells). On the other hand, normal skin was characterized by an intense membranous staining for beta-catenin, with a progressive displacement of the signal toward the periphery of the cells. In BCC the absence of membrane localization and cytosolic staining for beta-catenin were detected in de-differentiated cases. A significant correlation (by Pearson's analysis) between overexpression of WNT-1 and free pools of beta-catenins was observed in these tumors.


CONCLUSIONS
According to these data, the potential role of the WNT-1 gene in BCC seems to correlate with its ability to induce elevated cytoplasmic beta-catenin levels, suggesting that the WNT-1 gene can activate an intracellular signaling pathway involved in the process of cell transformation.
Lo Muzio
Lorenzo
L
Institute of Dental Sciences, University of Ancona, Italy. llomuzio@tin.it
Pannone
Giuseppe
G
Staibano
Stefania
S
Mignogna
Michele D
MD
Grieco
Michele
M
Ramires
Pierangela
P
Romito
Anna Maria
AM
De Rosa
Gaetano
G
Piattelli
Adriano
A
D000328:Adult; D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000502:physiology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D012867:Skin / Q000378:metabolism; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin