E-cadherin and β-catenin expression in well-differentiated and moderately-differentiated oral squamous cell carcinoma: relations with clinical variables

The aim of this study was to establish the expression and localisation of E-cadherin and β-catenin in oral squamous cell carcinomas (SCC) so that we could correlate the findings with prognostically-relevant clinicopathological variables. E-cadherin and β-catenin expression in normal oral mucosa and in oral squamous cell carcinomas were examined immunohistochemically, and their association with clinicopathological factors and prognosis were then analysed in 69 patients who had been operated on for oral SCC. E-cadherin expression was found in all 69 cases: in 11 cases (16%) it was weak; in 21 (30%) moderate, and in 37 (54%) high. β-Catenin expression was found in 64 cases (93%): in 18 cases (26%) cell-membrane expression was weak; in 26 (38%) it was moderate; in 19 (28%) it was high, and in one case (1%) there was cytoplasmic staining. No nuclear staining was detected. E-cadherin was significantly associated with histological grade (p = 0.002) and alcohol consumption (p = 0.05), and β-catenin was significantly associated with nodal stage (p = 0.02), TNM stage (p = 0.009), and E-cadherin expression (p = 0.01). However, none of them were independent prognostic factors in the disease-specific survival analysis. E-cadherin is closely linked to β-catenin expression in oral SCC and to tumour differentiation. Alcohol consumption could increase the aggressiveness of SCC, leading to reduced expression of E-cadherin. β-catenin could be an early marker for the identification of occult metastases in patients with oral SCC.     

Altered β-catenin expression in oral mucosal dysplasia: a comparative study

Objective

The current study aimed to investigate the β-catenin expression in oral leukoplakia (OL) with different degrees of epithelial dysplasia and normal oral mucosa.

Material and Methods

Formalin-fixed, paraffin-embedded tissue samples of 39 OL (mild dysplasia n=19, moderate dysplasia n=13, and severe dysplasia n=7), and 10 normal oral mucosa (control group) were submitted to immunohistochemical reactions to anti-β-catenin primary antibody. A qualitative β-catenin analysis was performed based on the percentage of positive cells. The cellular location and the epithelial layer were also considered. The Chi-square test and the Fisher’s exact test were used to verify possible differences in the β-catenin expression among the OL groups. A p-value of <0.05 was considered statistically significant.

Results

Membranous expression of β-catenin in parabasal and basal layers was gradually lost in the higher degrees of epithelial dysplasia. In normal oral mucosa, β-catenin was detected only in the cytoplasmic membrane. However, a significant increase in cytoplasmic β-catenin could be observed between mild and moderate dysplasia (Fisher Exact test - p<0.001) and between mild and severe dysplasia (p<0.001).

Conclusions

The β-catenin cytoplasmic expression observed in this study may represent the initial stage of modifications in the E-cadherin-catenin complex, along with morphological cellular changes.     

The immunohistochemical profile of basal cell nevus syndrome–associated and sporadic odontogenic keratocysts: a systematic review and meta-analysis

Clinical Oral Investigations - To provide a systematic review of the literature on studies comparing the immunoprofile of nevoid basal cell carcinoma syndrome (BCNS)–associated and sporadic...     

The role of integrin β1 in human dental pulp cell adhesion on laminin and fibronectin

Objective. This study is to identify the expression of integrin β₁ in human dental pulp cells and the role of integrin β₁ in pulp cell adhesion on extracellular matrix protein laminin and fibronectin.Study design. Immunoblot detection of integrin β₁ in human dental pulp cells was with the use of monoclonal anti-β₁ antibody. Dental pulp cell adhesion assay on extracellular matrix protein laminin and fibronectin and blocking cell adhesion was performed with monoclonal anti-β₁ antibody.Result. Integrin β₁ was identified in human dental pulp cells. Pulp cells adhered and spread on both laminin and fibronectin. Monoclonal anti-β₁ antibody inhibited human dental pulp cells adhesion on laminin but not on fibronectin.Conclusions. Integrin β₁ was expressed on human dental pulp cells and mediated cell adhesion on laminin. Human dental pulp cells also adhered on fibronectin but the adhesion was not regulated by β₁ integrin.     

Aberrant expression of β-catenin and its association with ΔNp63, Notch-1, and clinicopathological factors in oral squamous cell carcinoma

The present study focuses on the correlation between the expression pattern of β-catenin (component of Wnt signaling), ΔNp63 (proliferation marker), and Notch 1 (transmembrane receptor) in oral squamous cell carcinoma. The study also aims to investigate the interaction between β-catenin and ΔNp63 in oral cancer. Furthermore, we also analyzed the prognostic significance of β-catenin, ΔNp63, and Notch 1 in oral squamous cell carcinoma. Immunohistochemical analysis of β-catenin, ΔNp63, and Notch 1 were done in 62 cases of oral squamous cell carcinoma. Co-immunoprecipitation analysis was done to study the possible interaction between β-catenin and ΔNp63 in oral cancer. Kaplan-Meier method was used to estimate overall and disease-free survival, and the Log-rank test was used to compare the resulting curves. Statistically significant positive correlation was found between the localization of β-catenin and the expression of ΔNp63 (p = 0.001**, r (s) = 0.427), whereas, no significant association was found between the expression pattern of β-catenin and Notch 1. Interestingly, interaction between β-catenin and ΔNp63 was observed in oral carcinoma. Moreover, β-catenin and ΔNp63 may be related to worst survival in oral carcinoma. Statistically significant positive association between localization of β-catenin and expression of ΔNp63 suggests that they might have dependent roles in maintaining the proliferation of oral carcinoma cells. In addition, the downregulated expression of Notch 1 was related to invasion and differentiation status of oral carcinoma cells. Furthermore, β-catenin and ΔNp63 may be used as independent prognostic markers of oral carcinoma. On the other hand, interaction of β-catenin with ΔNp63 may be a key event in maintaining the proliferation of oral carcinoma cells. The present study indicates that β-catenin and ΔNp63 may be used as independent prognostic markers of oral carcinoma and the interaction of β-catenin with ΔNp63 may be a crucial event in regulating proliferation and differentiation of oral carcinoma cells, which may be used as a target for therapeutic implications.     

Immunohistochemical expression of podoplanin in so-called hard α-keratin-expressing tumors, including calcifying cystic odontogenic tumor, craniopharyngioma, and pilomatrixoma

Podoplanin, a transmembrane sialomucin-like glycoprotein, is a specific marker of lymphatic vessels, and its expression is also considered to be associated with tumor invasion and tooth development. In this study, we examined the expression of podoplanin in calcifying cystic odontogenic tumor (CCOT) in comparison with that in other so-called hard α-keratin-expressing tumors such as craniopharyngioma (CP) and pilomatrixoma (PM). Immunohistochemical staining for podoplanin was carried out using surgical specimens of 15 CCOTs of the jaw, 19 CPs of the pituitary gland, and 15 PMs of the skin. Positivity for hard α-keratin was evident in ghost, shadow and transitional cells in all of these tumors (100%). The podoplanin expression in CCOTs was evident in the periphery of ameloblastoma-like epithelium (86.6%) and the epithelial cells adjacent to ghost cells (60%). On the other hand, in adamantinomatous-type CPs, podoplanin expression was observed in epithelial components corresponding to the stratum intermedium (100%), but not in the periphery of ameloblastoma-like epithelium (0%). In squamous-type CPs podoplanin was expressed in basal cells (100%), but all of the PMs were podoplanin-negative (0%). In the periphery of the ameloblastoma-like epithelium or basophilic cell layer, podoplanin was expressed more strongly in CCOTs than in CPs or PMs. These findings suggest that the expression of podoplanin in CCOTs may reflect rapid turnover of cytoskeletal filaments and local invasiveness.     

Two modifications in the treatment of keratocystic odontogenic tumors (KCOT) and the use of Carnoy’s solution (CS)—a retrospective study lasting between 2 and 10 years

This retrospective study aimed at evaluating the recurrence rates of keratocystic odontogenic tumors (KCOTs) that were enucleated with and without the application of Carnoy’s solution (CS). The study included 36 KCOTs treated between 1996 and 2006. Recurrence rates were investigated in correlation with the respective treatment method applied. Additionally, any damage to the inferior alveolar nerve associated with treatment was analyzed. Treatments consisted of enucleation with (38.9%) or without (61.1%) the application of CS. Median follow-up was 4.5 years. Single enucleation showed a recurrence rate of 50%, but the additional application of CS reduced the recurrence rate to 14.3%. No detrimental effects of CS on the mandibular nerve were detected. Enucleation plus the application of CS reduced the recurrence rate of KCOTs compared with simple enucleation. The application of CS did not cause any damage to the mandibular nerve.     

Maresin 1 regulates autophagy and inflammation in human periodontal ligament cells through glycogen synthase kinase–3β/β-catenin pathway under inflammatory conditions

ObjectiveAccumulating lines of evidence suggest that maresin 1 (MaR-1) exerts anti-inflammatory effects in many cell types and plays beneficial roles in inflammatory disease, such as peritonitis and colitis. Moreover, it has been demonstrated that MaR-1 play protective roles against localized aggressive periodontitis. However, the function and mechanism of MaR-1 in human periodontal ligament cells (PDL) cells from periodontitis are poorly understood. The present study aimed to clarify the effects and molecular mechanism of MaR-1 in PDL cell survival and inflammation.MethodsPDL cells were isolated from the middle third of the root surface of premolars from four healthy humans; MTT assay and cell death detection ELISA assay were used to detect cell survival and apoptosis; Inflammatory cytokines level was measured by ELISA assay; RT-PCR and western blot was used to measure the mRNA and protein expression in this study.ResultsHere we found that MaR-1 treatment markedly promotes survival and inhibits apoptosis in PDL cell treated by LPS. MaR-1 treatment strikingly suppressed the production of LPS-induced pro-inflammatory cytokines IL-6, IL-8, TNF-α and IL-1β. MaR-1 also promotes autophagy by increasing the ratio of LC3II/LC3I, the level of beclin-1 and reduced the expression of p62 in LPS treated PDL cells, which is beneficial to cell survival. Moreover, the results showed that MaR-1-mediated autophagy is dependent on the glycogen synthase kinase–3β(GSK-3β)/β-catenin signal pathway. The inhibitor of autophagy 3-MA and the inhibitor of the GSK-3β/β-catenin signal pathway LiCL both reverse the effects of MaR-1 on LPS-treated PDL cell survival and inflammation.ConclusionMaR-1 promotes cell survival and alleviates cell inflammation by activating GSK-3β/β-catenin-dependent autophagy. These results provide new insights into the mechanism of chronic periodontitis.     

Root lesions in a group of 50–60 year-old Germans related to clinical and social factors

From a preventive point of view collection of data concerning carious and non-carious cervical tooth defects is definitely important. Consequently, the prevalence and distribution of different root lesions were studied and correlated with behavioral and biological factors in 50- to 60-year-old German individuals (n=298). Additionally, the data were correlated with characteristics concerning oral health and known risk factors such as gender, educational level, and presence of plaque. An interview included questions on sociodemographic and socioeconomic characteristics, dental and general health status, and various behavioral parameters. During clinical examination data concerning coronal and root lesions, restorations, probing depth, gingival bleeding, and dental plaque were obtained. The participants represented a social middle class population with a high awareness of dental health. Obviously, for the participants, known risk factors for root decay such as gender, educational level and plaque index were of minor importance. Factors correlating with root caries were: (a) number of missing teeth, (b) probing depth, (c) smoking habit, (d) regular dental attendance and (e) the reason for the last dental treatment. Additionally, the prevalence of non cariogenic lesions, primarily resulting from increased but wrongly performed oral self care, seems gradually to relieve carious root destruction. Received: 22 June 1999 / Accepted: 24 August 1999     

Association of a genetic polymorphism (-44 C/G SNP) in the human DEFB1 gene with expression and inducibility of multiple β-defensins in gingival keratinocytes

Background  

Human β-defensins (hBDs) are antimicrobial peptides with a role in innate immune defense. Our laboratory previously showed that a single nucleotide polymorphism (SNP) in the 5' untranslated region of the hBD1 gene (DEFB1), denoted -44 (rs1800972), is correlated with protection from oral Candida. Because this SNP alters the putative mRNA structure, we hypothesized that it alters hBD1 expression.