Increased nuclear β-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

Abstract

BackgroundDeregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Material and MethodsCross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used.ResultsNuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05).ConclusionsOur results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia.

Nuclear accumulation of β‐catenin is associated with endosomal sequestration of the destruction complex and increased activation of Rab5 in oral dysplasia

“…By focusing in oral lesions, we and others have observed that β-catenin is progressively accumulated in the nucleus of dysplastic cells, as shown in cultured DOK and patient biopsies. 9,10 In fact, our more recent studies demonstrate that nuclear accumulation of β-catenin gradually augments from mild through moderate and severe dysplasia, and that these changes are associated with augmented Wnt3a in tissue biopsies. 12 Aside the requirement of Wnt ligands for nuclear accumulation of β-catenin in malignancy, 39,40 no information is available regarding molecular mechanisms involved in aberrant stabilization of β-catenin in premalignant lesions.…”

“…The latter is important, based on the ability of Rab5 to control early endosome dynamics, which may impinge in the acquisition of malignant traits in tumor cells, and most importantly, in oral dysplasia. In this context, the accumulation of nuclear β‐catenin in tumor cells and in oral dysplasia is striking, since these phenomena could be due to increased endosomal targeting of the β‐catenin destruction complex. Here, we explored whether endosomal sequestration of the destruction complex accounts for increased accumulation of nuclear β‐catenin in oral dysplasia and assessed the role of the endocytic protein, Rab5, in these events.…”

“…Specifically, it has been shown that components of the Wnt/β-catenin signaling pathway are upregulated in mild and severe oral dysplasia. [9][10][11] Accordingly, recent studies from our laboratory showed that increased Wnt3a secretion in oral dysplasia leads to nuclear accumulation of β-catenin and Tcf/Lef-dependent transcription of target genes upregulated in oral dysplasia, as shown in patient biopsies and in cell culture models, using dysplastic oral keratinocytes (DOK) and primary cultures of nontumor oral keratinocytes. 12 Nevertheless, the mechanisms involved in nuclear translocation of β-catenin in oral dysplasia remain unclear.…”

The Role of Carcinogenesis-Related Biomarkers in the Wnt Pathway and Their Effects on Epithelial–Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma

“…After activation of canonical WNT signaling, cytoplasmic β-catenin dissociates from the cadherin-catenin protein complex, translocates, and accumulates in the nucleus, where β-catenin interacts with TCF/LEF to induce downstream gene expression ( Figure 3). In this way, cell proliferation, migration, or invasion can be affected [60].…”

Prognostic value of the immunohistochemical detection of epithelial-mesenchymal transition biomarkers in oral epithelial dysplasia: A systematic review

“…After reading the titles and abstracts, 54 studies were considered potentially eligible and their full text was read by three reviewers. Seventeen articles met all inclusion criteria and were selected for this systematic review (5,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). The selected articles were observational studies published between 2007 and 2018, all of them in English.…”