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

Abstract

Background: Deregulation of β-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 β-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC).

Material and methods: Cross sectional study. Immunodetection of β-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.

Results: Nuclear expression of β-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).

Conclusions: Our results are consistent with most of the reports which show increased presence of β-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear β-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 β-catenin could be a possible immune marker in the detection of oral dysplasia.

Figure 1

Samples of normal oral mucosa (A), mild dysplasia (C) with hematoxylin-eosin staining. Immunohistochemical localization of Ki-67 at the basal strata of the epithelium in normal oral mucosa (B), in mild dysplasia the protein locates mainly in the lower third of the epithelium (D). Samples of moderate (E) and severe dysplasia (G) with hematoxylin-eosin staining. Immunohistochemical localization of Ki-67 in moderate dysplasia (F) the nuclear expression of Ki-67 is located at the medium and lower third of the epithelium; severe dysplasia (H) immunohistochemical localization of Ki-67 at the lower, medium and higher thirds of the epithelium.

Figure 2

Samples of well differentiated OSCC (I), moderate differentiated OSCC (K) and poorly differentiated OSCC (M) with hematoxylin-eosin staining. Immunolocalization of Ki-67 in well differentiated OSCC (J); moderate differentiated OSCC (L) and poorly differentiated OSCC (N) is observed in all epithelia strata.

Figure 3

Immunohistochemical localization of ?-catenin in normal oral mucosa (A-B), in which only membrane expression is observed; mild dysplasia (C-D), where the protein is mainly localized at membrane and cytoplasm and the nuclear expression is present but at the lowest degree (D). Immunohistochemical localization of ?-catenin in moderate dysplasia (E-F), where the nuclear expression of ?-catenin is greater; severe dysplasia (G-H) where the protein strongly expressed at the lower layers of the epithelium.

Figure 4

Immunohistochemical localization of ?-catenin in well diferentiated OSCC (I-J), the protein is primarily localized at membranous and cytoplasmic level, the nuclear expression is very low: moderately differentiated OSCC (K-L), the membrane protein expression is lost to a lesser degree of differentiation, as in the poorly differentiated OSCC samples where no nuclear expression of ?-catenin observed (M-N).