Imunoexpressão das claudinas -1 e -7 em ameloblastomas e germes dentais humanos

We investigated the immunohistochemistry expression of claudins -1 and -7 in ameloblastoma and in human dental germs on the pattern of distribution (focal, regional or diffuse), the cells that expressed (if central or peripheral) and the location of that expression in the cell components recital membrane, cytoplasm and nucleus. Among the 29 cases of ameloblastoma, 24 were type solid and 6 unicystic. In 7 mandibular specimens of human fetuses found dental germs from the stage of bud to the crown. We note that the pattern of expression in the dental germs was variable for claudinas studied according to the cell type and stage of differentiation and was invariate only in the cells of stellate reticulum. In epithelium internal of enamel organ, claudin-1 has been decreasing with the progression of differentiation as to claudina-7 that was found in the cells of the peripheral papilla. For ameloblastoma the expression was more significant than that observed in dental germs. Fisher s exact test no found association between the expression of claudinas cells in central and peripheral and the type of ameloblastoma (solid or unicystic). Thus, in general the claudin-1 was positive in the central cell of 93,1% of the cases and in peripheral cells of 51,7%. The claudin-7 was expressed in the cells of all cases central and peripheral cells from 89,7%. For both claudins the distribution was predominantly diffuse cells both in central and peripheral cells. Given our findings it is suggested that the expression of claudins may be indicative of the involvement of these molecules in morphogenetics events culminating with the dental development and that possibly influence the development of neoplastic ameloblastoma

Avaliação imuno-histoquímica da BMP-2, BMP-4 e seus receptores (BMPRIA e BMPRII) em ameloblastomas e tumor odontogênico adenomatóide

BMPs are components superfamily ligands transformation growth fator-β (TGF-β) secreted into the extracellular environment, with mechanisms of intercellular communication through specific ligands and receptors in various target cells, being recognized for its influence in osteogenic induction, also play an important role in tissue homeostasis, cell proliferation, differentiation control , in addition to being present in the development of various malignancies. The aim of this study was to compare the immunohistochemical expression of BMP-2, BMP-4 and its receptors BMPRIA and BMPRII in cases of ameloblastoma and adenomatoid odontogenic tumor. The sample consisted of 20 cases of solid ameloblastoma (SA), 10 cases of ameloblastoma unicystic (UA) and 16 cases of adenomatoid odontogenic tumor (AOT). The expression of BMPs and their receptors was evaluated in the parenchyma and stroma of lesions, establishing the percentage of immunopositive cells (0 - negative; 1-1 % to 10 % of cells positive; 2 - 11% to 25% of positive cells; 3 - 26% to 50% of cells positive; 4 - 51% to 75 % of positive cells; 5 - more than 75% positive cells). Analysis of the expression of BMP-2 revealed no statistically significant differences in parenchymal (p = 0.925) and stromal component (p = 0.345) between the groups, as well as BMP-4 (p = 0.873 / p = 0.131). In the epithelial component, SA and AOT had a higher frequency of score 5. In turn, all cases of UA were classified as score 5. The analysis of the stromal component showed no statistically significant difference between groups with respect to median scores BMPRIA positivity (p = 0.768) and BMPRII (p = 0.779). In the epithelial component of SA and UA, no statistically significant correlations between imunoexpression proteins analyzed were observed. In turn, the group of AOT, statistically significant positive correlations between the scores of expression of all studied proteins were found. In the stromal component, statistically significant positive correlations were found only in the SA group in BMP -4 and BMPRII (r = 0.476; p = .034), in the UA in BMP-4 and BMPRIA (r = 0.709; p = 0.022). The results of this study suggest that the BMPs and their receptors are involved in the development process odontogenic tumors. BMP-4, in turn, besides being present in odontogenic tumors have the capacity to form mineralized material.

Estudo imuno-histoquímico da presença de miofibroblastos e da expressão do fator transformador de crescimento-beta1, interferon gama, metaloproteinase de matriz 13 e indutor de metaloproteinases de matriz em lesões odontogênicas epiteliais

Myofibroblasts are cells that exhibit a hybrid phenotype, sharing the morphological characteristics of fibroblasts and smooth muscle cells, which is acquired during a process called differentiation. These cells then start to express -SMA, a marker that can be used for their identification. Studies suggest that myofibroblasts are related to the aggressiveness of different tumors and that TGF-1 and IFN- play a role in myofibroblast differentiation, stimulating or inhibiting this differentiation, respectively. The objective of this study was to investigate the role of myofibroblasts in epithelial odontogenic tumors, correlating the presence of these cells with the aggressiveness of the tumor. Immunohistochemistry was used to evaluate the expression of TGF-1 and IFN- in myofibroblast differentiation, as well as the expression of MMP-13, which is activated by myofibroblasts, and of EMMPRIN (extracellular matrix metalloproteinase inducer) as a precursor of this MMP. The sample consisted of 20 solid ameloblastomas, 10 unicystic ameloblastomas, 20 odontogenic keratocysts, and 20 adenomatoid odontogenic tumors. For evaluation of myofibroblasts, anti- -SMA-immunoreactive cells were quantified in connective tissue close to the epithelium. Immunoexpression of TGF-1, IFN-, MMP-13 and EMMPRIN was evaluated in the epithelial and connective tissue components, attributing scores of 0 to 4. The results showed a higher concentration of myofibroblasts in solid ameloblastomas (mean of 30.55), followed by odontogenic keratocysts (22.50), unicystic ameloblastomas (20.80), and adenomatoid odontogenic tumors (19.15) (p=0.001). No significant correlation between TGF-1 and IFN- was observed during the process of myofibroblast differentiation. There was also no correlation between the quantity of myofibroblasts and MMP-13 expression. Significant correlations were found between MMP-13 and TGF-1 (r=0.087; p=0.011), between MMP- 13 and IFN- (r=0.348; p=0.003), as well as between EMMPRIN and MMP-13 (r=0.474; p<0.001) and between EMMPRIN and IFN- (r=0.393; p=0.001). The higher quantity of myofibroblasts observed in solid ameloblastomas, odontogenic keratocysts and unicystic ameloblastomas suggests that these cells are one of the factors responsible for the more aggressive biological behavior of these tumors, although the myofibroblast population was not correlated with TGF-1, IFN-, MMP-13 or EMMPRIN. The correlation between MMP- 13 and TGF-1 suggests that the latter induces the expression of this metalloproteinase. The present results also support the well-established role of EMMPRIN as an inducer of MMP-13. Furthermore, the relationship between EMMPRIN and IFN- and between MMP-13 and IFN- suggests synergism in the antifibrotic effect of these markers

Immunohistochemical expression of E-cadherin and beta-catenin in ameloblastomas and tooth germs

OBJECTIVE: The aim was to analyze the expression of E-cadherin and beta-catenin in ameloblastomas and tooth germs to determine their roles in cell differentiation processes and invasiveness compared with odontogenesis. STUDY DESIGN: Twenty-one ameloblastoma cases (16 solid and 5 unicystic tumors) and 5 tooth germs were submitted to the immunohistochemical detection of E-cadherin and beta-catenin. Immunoreactivity was evaluated using descriptive and semiquantitative analysis, investigating the location and intensity of staining. The Fisher exact test was performed, and P values of <.05 were considered to indicate statistical significance. RESULTS: There was no statistically significant difference in the expression of E-cadherin and beta-catenin between solid and unicystic ameloblastomas (P = .59; P = .63; respectively). The same was found when comparing solid and unicystic ameloblastomas with the tooth germs for both E-cadherin (P = .53; P = .44; respectively) and beta-catenin (P = .12; P = .16; respectively). Nuclear staining of beta-catenin was observed in only 4 cases (3 solid and 1 unicystic tumor). CONCLUSION: The results showed no differences in the expression of E-cadherin or beta-catenin between tooth germs and solid and unicystic ameloblastomas. The expression of these molecules seems mainly to be related to the process of cell differentiation.

Immunoexpression of integrins in ameloblastoma, adenomatoid odontogenic tumor, and human tooth germs

The expression of integrins alpha2beta1, alpha3beta1, and alpha5beta1 in 30 ameloblastomas (20 solid and 10 unicystic tumors), 12 adenomatoid odontogenic tumors (AOTs), and 5 human tooth germs in different stages of odontogenesis was analyzed. The distribution, location, pattern, and intensity of immunohistochemical expression were evaluated. Intensity was analyzed using scores (0 = absence, 1 = weak staining, and 2 = strong staining). No difference in the immunoexpression of the integrins was observed between solid and unicystic ameloblastomas. When these two ameloblastoma types were pooled into a single group, the following significant differences were found: immunoexpression of integrin alpha2beta1 was stronger in ameloblastomas than in AOTs and tooth germs, and the expression of integrin alpha5beta1 was stronger in ameloblastomas than in AOTs. The lack of detection of integrin alpha3beta1 in tooth germs and its detection in the odontogenic tumors studied suggest that this integrin might be used as a marker of neoplastic transformation in odontogenic tissues.

Immunoexpression of integrins in ameloblastoma, adenomatoid odontogenic tumor, and human tooth germs

The expression of integrins alpha2beta1, alpha3beta1, and alpha5beta1 in 30 ameloblastomas (20 solid and 10 unicystic tumors), 12 adenomatoid odontogenic tumors (AOTs), and 5 human tooth germs in different stages of odontogenesis was analyzed. The distribution, location, pattern, and intensity of immunohistochemical expression were evaluated. Intensity was analyzed using scores (0 = absence, 1 = weak staining, and 2 = strong staining). No difference in the immunoexpression of the integrins was observed between solid and unicystic ameloblastomas. When these two ameloblastoma types were pooled into a single group, the following significant differences were found: immunoexpression of integrin alpha2beta1 was stronger in ameloblastomas than in AOTs and tooth germs, and the expression of integrin alpha5beta1 was stronger in ameloblastomas than in AOTs. The lack of detection of integrin alpha3beta1 in tooth germs and its detection in the odontogenic tumors studied suggest that this integrin might be used as a marker of neoplastic transformation in odontogenic tissues.