Nuclear localization of beta-catenin involved in precancerous change in oral leukoplakia

Kosei Ishida, Satoshi Ito, Naoyuki Wada, Hiroyo Deguchi, Tsuyoshi Hata, Masaru Hosoda, Tsutomu Nohno, Kosei Ishida, Satoshi Ito, Naoyuki Wada, Hiroyo Deguchi, Tsuyoshi Hata, Masaru Hosoda, Tsutomu Nohno

Abstract

Background: Oral leukoplakia is a precancerous change developed in the oral mucosa, and the mechanism that oral leukoplakia becomes malignant through atypical epithelium is not known. Here we compared the beta-catenin expression detected by immunohistochemical staining in the normal oral epithelium and in the oral leukoplakia with or without dysplasia.

Results: The normal oral epithelium showed beta-catenin expression only in the cell membrane, but not in the nuclei. In the oral leukoplakia without dysplasia, 7 out of 17 samples (41%) showed beta-catenin expression in the cell membrane, and 5 samples (29%) showed expression in the nuclei. In the oral leukoplakia with dysplasia, nuclear expression of beta-catenin was shown in 11 out of 12 samples (92%). Incidence of nuclear beta-catenin expression was significantly different between dysplasia and normal oral epithelium (P < 0.01), and also between oral leukoplakia with dysplasia and those without dysplasia (P < 0.01). Wnt3 expression was detected in the epithelial cell membrane or cytoplasm in oral leukoplakia where nuclear expression of beta-catenin was evident, but not in epithelial cells without nuclear expression of beta-catenin.

Conclusion: The components of canonical Wnt pathway, such as Wnt3, beta-catenin, and cyclin D1, were detected, implying that this pathway is potentially involved in the progression of dysplasia in oral leukoplakia.

Figures

Figure 1
Figure 1
Immunohistochemical localization of β-catenin in normal oral epithelium (a-c), oral leukoplakia without dysplasia (d-f), oral leukoplakia with mild dysplasia (g-i), oral leukoplakia with severe dysplasia (j-l), and oral squamous cell carcinoma (m-o). (a, d, g, j) Hematoxylin and eosin staining. (b, c, e, f, h, i, k, l, m-o) β-Catenin staining. (b, c) Signals were detected in the cell membrane of the basal and spinous layer, but not in the cytoplasm and nuclei. (e, f) Signals were detected in the cell membranes and cytoplasm. (h, i) Signals were detected in the cell membranes and nuclei. (j) The area for dysplasia is characterized by an increased nuclear-cytoplasmic ratio, an increased number of mitotic figures, including abnormal mitoses, nuclear hyperchromatism. (k, l) Signals were detected in the cell membranes and nuclei. (m-o) Signals were detected in the nucleus of the epithelial dysplastic cells (n) and carcinoma cells (o) in OSCC, but cell membranous expression was weak or absent. Scale bars: (a, b, d, e, g, h, j, k, m) 200 μm; (c, f, i, l, n, o) 50 μm.
Figure 2
Figure 2
Comparison of immunohistochemical staining for β-catenin, Wnt3, cyclin D1, and c-myc in oral leukoplakia. (a-d) Serial sections of oral leukoplakia without dysplasia. (a) Nuclear expression of β-catenin was not observed. (b) Wnt3 expression was not observed. (c) Cyclin D1 shows weak expression. (d) Nuclear expression of c-myc is observed in the basal layer cells. (e-h) Serial sections of oral leukoplakia with dysplasia. (e, i) β-Catenin is expressed in the nuclei. (f, j) Wnt3 expression is observed on the epithelial cell membrane and in the cytoplasm. (g, k) Cyclin D1 is expressed in several epithelial cells. (h, l) c-Myc shows similar expression pattern as oral leukoplakia without dysplasia. Scale bars: (a-h) 100 μm; (i-l) 50 μm.
Figure 3
Figure 3
Relationship between subcellular localization of β-catenin and expression patterns of cyclin D1 and c-myc in oral leukoplakia. Shown by means with standard deviations.

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