CD1a-positive Langerhans cells and their relationship with E-cadherin in ameloblastomas and keratocystic odontogenic tumors.

Ameloblastomas and keratocystic odontogenic tumors (KOTs) are lesions that are characterized by locally invasive growth and cause extensive bone destruction. In addition, it is known that E-cadherin influences the adhesion of Langerhans cells (LCs) to keratinocytes. The aim of this study was to investigate, using immunohistochemistry, the distribution of CD1a-positive cells in ameloblastomas and KOTs and their relationship with E-cadherin, in comparison to calcifying cystic odontogenic tumor (CCOT). The CD1a-positive LCs were observed in 11 ameloblastomas and KOTs. All of the cases of CCOT showed CD1a-positive LCs and a significant difference was found when this tumor was compared with ameloblastomas (P < 0.05, Mann-Whitney test). A statistically significant difference was also noted when comparing CD1a-positive LCs between CCOTs and KOTs (P < 0.05, Mann-Whitney test). Lower expression of E-cadherin in ameloblastomas (AMs) in relation to KOTs and CCOTs (P < 0.05, Fisher test) was observed. There was no correlation between E-cadherin and CD1a-positive LCs between all odontogenic tumors that were studied (P > 0.05, Spearman test). A quantitative difference of CD1a-positive cells between AMs and KOTs in comparison to CCOTs was observed. This permits to speculate that a depletion of CD1a-positive LCs might influence the local invasiveness of ameloblastomas and KOTs. Furthermore, it is suggested that E-cadherin mediates cell adhesion in these tumors.

Mello LA ，Figueiredo AL ，Ramos EA ，Gurgel CA ，Martins MD ，de Figueiredo CR ，Cury PR ，de Albuquerque Júnior RL ，Ramalho LM ，Santos JN ... -  《-》

Immunohistochemical assessment of CD1a-positive Langerhans cells and their relationship with E-cadherin in minor salivary gland tumors.

The aim of this study was to investigate the presence of CD1a-positive Langerhans cells and their relationship with E-cadherin in minor salivary gland tumors. Twenty-seven minor salivary gland tumors were investigated using immunohistochemistry for CD1a and E-cadherin. A significant difference regarding the mean density of CD1a-positive Langerhans cells was observed between pleomorphic adenomas and malignant tumors studied (P = 0.001). No CD1a-positive cells were detected in most cases (n = 5) of cystic adenoid carcinomas. CD1a-positive cells were detected in one mucoepidermoid carcinoma case, and six low-grade polymorphous adenocarcinomas cases. Comparison of the mean density of CD1a-positive cells between the three malignant tumors showed no significant difference (P = 0.127). No significant difference was observed in the presence of E-cadherin between tumors (P = 0.73), but it was detected in 24 cases. The lack of CD1a-positive in malignant salivary gland tumors facilitates the neoplastic development and suggests that these cells might be useful as auxiliary diagnostic and prognostic tool in minor salivary gland tumors. Furthermore, it is suggested that E-cadherin mediates cell adhesion in these tumors although we did not demonstrate significance.

Dultra FK ，Barros AC ，Schaer-Barbosa H ，Figueiredo AL ，Gurgel CA ，Ramos EA ，da Silva Carvalho AM ，dos Santos JN ... -  《-》

Syndecan-1 (CD 138) surface expression marks cell type and differentiation in ameloblastoma, keratocystic odontogenic tumor, and dentigerous cyst.

The altered expression of syndecan-1 (SD-1), a transmembrane heparan sulfate proteoglycan, in ameloblastomas and cysts of odontogenic origin suggests that this molecule could have prognostic value in assessing the clinical outcome of those lesions. The purpose of this study was to analyze SD-1 expression profile immunohistochemically in archival, paraffin-embedded tissue sections of ameloblastomas and in common odontogenic cysts arising from the same locale. SD-1 expression was investigated in 32 ameloblastomas, 26 keratocystic odontogenic tumors (KCOT), and 21 dentigerous cysts from the archives of the histopathology laboratory which were routinely processed. The cases were reviewed and assessed according to the established criteria. Sections were immunostained with monoclonal antibody against SD-1 (CD138). Sections of normal oral mucosa, site matched, were stained in parallel as positive controls. The plasma cells in sections served as internal positive controls. SD-1 expression was observed in the epithelial and stromal elements of the sections, and the expression was significantly associated with the lesion's extension and involvement of adjacent structures (P=0.025). Stellate-reticulum cells showed higher expression than the ameloblasts, which was at a significant level (P<0.0001). Highly significant difference was reported among the three groups of lesion for the epithelial staining (P<0.0001). The mean rank scores (Kruskal-Wallis test) of ameloblastomas were significantly lower than those of KCOT and dentigerous cysts. Non-significant comparison was made between KCOT and dentigerous cyst groups. The present study revealed SD-1 immunoreactivity in the stromal cells of ameloblastoma, KCOT, and dentigerous cysts rather uniformly. This reported SD-1 expression by the tumor stroma is considered to be associated with poor prognosis of the lesions.

Al-Otaibi O ，Khounganian R ，Anil S ，Rajendran R ... -  《-》

E-cadherin-dependent adhesion of dendritic and Langerhans cells to keratinocytes is defective in cervical human papillomavirus-associated (pre)neoplastic lesions.

Although human papillomavirus (HPV) DNA is detected in the majority of squamous intraepithelial lesions (SILs) and squamous cell carcinomas (SCCs) of the uterine cervix, the persistence and progression of cervical lesions suggest that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most SILs show quantitative and functional alterations of Langerhans cells (LCs). The aim of this study was to determine whether modulation of E-cadherin-mediated homophilic and heterotypic interactions between keratinocytes and LCs is involved in these abnormalities of LCs in (pre)neoplastic cervical epithelium. Cell membrane expression of E-cadherin and the density of CD1a+ LCs were low in the epithelium of SILs and SCC biopsy specimens, compared with normal exocervical epithelium. Dendritic cells (DCs) and LCs generated in vitro were randomly distributed throughout the full thickness of organotypic cultures of E-cadherin- HPV-transformed cells. In contrast, these cells rapidly adhered to the keratinocyte cell layers when HPV-transformed cells transfected with E-cadherin were used. These data suggest that the E-cadherin-mediated contact between keratinocytes and LCs is potentially important for initiating or maintaining the immune response during chronic HPV infection.

Hubert P ，Caberg JH ，Gilles C ，Bousarghin L ，Franzen-Detrooz E ，Boniver J ，Delvenne P ... -  《JOURNAL OF PATHOLOGY》

TGF-β1, Smad-2/-3, Smad-1/-5/-8, and Smad-4 signaling factors are expressed in ameloblastomas, adenomatoid odontogenic tumors, and calcifying cystic odontogenic tumors: an immunohistochemical study.

The TGF-β/Smad signaling pathway regulates diverse cellular functions, including tooth development, and is involved in numerous pathological processes such as tumorigenesis. The aim of this study was to investigate the immunoexpression of the TGF-β/Smad signaling pathway members in ameloblastoma (AM), calcifying cystic odontogenic tumor (CCOT), and adenomatoid odontogenic tumor (AOT). This retrospective cross-sectional study included 65 tissue specimens: 34 AMs, 13 CCOTs, and 18 AOTs. Serial sections were immunohistochemically stained with TGF-β1, Smad-4, Smad-1/-5/-8, and Smad-2/-3 antibodies, and a semiquantitative measurement of the positive cells was carried out by two oral pathologists using a 0-3 scale (0: no immunoreactivity, 1: <20% positive cells, 2: 20-50% positive cells, 3: >50% positive cells). All biomarkers studied were found significantly decreased in AM compared to CCOT and AOT. AOT and CCOT expressed Smad-1/-5/-8 more strongly compared to AM (OR = 11.66, P < 0.001 and OR = 5.34, P = 0.013, respectively), and Smad-2/-3 immunostaining was found significantly increased in CCOT (OR = 10.42, P = 0.001) and AOT (OR = 5.16, P < 0.004) compared to AM. Similarly, Smad-4 was expressed more strongly in AOT and CCOT compared to AM (P = 0.001), while AOT demonstrated a fivefold higher chance to express TGF-β1 compared to AM (P = 0.011). TGF-β/Smad signaling pathway is activated in AM, AOT, and CCOT. The statistically significant reduced TGF-β1/Smad immunoexpression in AM compared to AOT/CCOT could be associated with the more aggressive biological behavior of AM including increased cell proliferation and reduced apoptosis and differentiation. Thus, the biomarkers TGF-β, Smad-4, Smad-1/-5/-8, and Smad-2/-3 could serve as supplementary diagnostic indices between odontogenic tumors of high and low neoplastic dynamics.

Karathanasi V ，Tosios KI ，Nikitakis NG ，Piperi E ，Koutlas I ，Trimis G ，Sklavounou A ... -  《-》