Estudo da angiogênese pelo CD105 e FvW no carcinoma epidermóide oral e sua relação com o estadiamento clínico do tumor

The purpose of this study was to assess the immunohistochemical expression of CD105 and FvW antibodies in the angiogenesis of oral epidermoid carcinoma (OEC), correlating it with the TNM clinical staging system, seeking a better understanding of its biological behavior and use as an indicator of prognosis.The sample consisted of 30 epidermoid carcinoma (EC) cases, 10 of the floor of the mouth, 10 of the retromolar region and 10 of the tongue, in addition to 10 cases of pyogenic granuloma, which made up the control group. The results showed that mean microvessel counts (MVC) were correspondingly higher in the pyogenic granuloma group (CD105 = 57.26 vessels and FvW = 39.64) than in the EC group (CD105 = 10.09 and FvW = 12.20) and that the differences were statistically significant between the groups for each of the angiogenic biomarkers (p = 0.002 for CD105 and p< 0.001 for FvW). CD105 had better positivity in the pyogenic granuloma group (mean = 57.26 vessels) and for EC, FvW had the highest expression (mean = 12.20 vessels). With respect to EC, the most affected age group was between 51 and 70 years (n = 14; 46.7%), with a representative MVC for both markers. No statistically significant difference was found between the sexes for any of the markers (p = 0.967 for CD105 and p = 0.744 for FvW). Mean CD105 levels were much higher in patients with stage T3 and T4 (17.13) and lower in those with stage N+ (6.36). Mean FvW levels were higher in the patients with stage T1 and T2 (12.23) and lower in patients with T3 and T4 (12.10), but without a statistically significant difference. In regard to anatomic location, a statistically significant difference was observed between FvW sites, with a statistically significant difference between floor of the mouth cases and those located in the retromolar region (p =0.013). Therefore, this study suggests that CD105 expression in OEC angiogenesis, in contrast to other types of malignant neoplasias, may not be correlated with prognosis and tumor aggressiveness, whereas FvW was a more effective antibody for staining this lesion

Estudo imuno-histoquímico da expressão da glut-1 e mensuração do índice angiogênico (CD34) em adenomas pleomórficos, carcinomas adenóides císticos e carcinomas mucoepidermóides de glândulas salivares

The expression of glucose transporter protein 1 (GLUT-1), as well the angiogenesis has been associated to clinical behavior and aggressiveness in tumors of various origin. It is believed that the expression of this protein denotes metabolic demand of the tumor cells and, thus its influence upon the formation of new blood vessels. Pleomorphic adenoma (PA) and the adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) represent, respectively, the most commom benign and malignant tumors of salivary glands. The aim of this study was to analyze and compare the immunohistochemical expression of GLUT-1 and its correlation with angiogenesis in cases of PAs, ACCs and MECs considering their histological grades. The sample consisted of 20 PAs, 20 ACCs and 10 MECs. The cases were analyzed and classified according to their histological grades. The expression of GLUT-1 was evaluated in the parenchyma lesions, establishing the percentage of immunopositive cells, according to the following scores: 0 (no cell immunomarked), 1 (up to 25% of tumor cells immunostained), 2 (25 - 50% of tumor cells immunostained) and 3 (more than 50% of tumor cells immunostained). The angiogenic index was analyzed by counting the microvessels immunostained by anti-CD34 antibody, in 5 fields (200X). The analysis of the expression of GLUT-1 in tumor parenchyma showed statistically significant differences between benign and malignant groups (p = 0.022). The average number of microvessels in PAs was 40.4, 21.2 in ACCs and 66.5 in MECs, with significant differences between groups (p <0.001). When compared to the expression of GLUT-1 and angiogenic index as a whole, there was no significant correlation between the number of microvessels and the expression of GLUT-1 (r = 0.211, p = 0.141). In conclusion, the results of this study suggest not only that differences in biological behavior between PAs, ACCs and MECs may be associated to the expression of GLUT-1, but also that benign and malignant salivary gland present differences in the average number of microvessels, with higher levels considered more aggressive tumors. Furthermore, the number of newly formed microvessels can be independent of the metabolic demand of the tumor cells

Expressão imunoistoquímica de Glut-1 e marcadores de proliferação e apoptose em anomalias vasculares orais

Vascular anomalies constitute a distinct group of lesions, but they may present similar clinical and histopatological characteristics, which can lead to diagnostic mistakes. This study aimed by histopathology and immunohistochemical expression of human glucose transporter protein (GLUT-1), correctly identify and classify oral vascular anomalies, besides analyzing the immunoexpression of markers proliferation and apoptosis (Ki-67 and Bcl-2). All cases diagnosed as "oral hemangiomas" belonging to the archives of the Service of Pathological Anatomy from the subject of Oral Pathology of the Department of Dentistry (DOD), of the Federal University of Rio Grande do Norte (UFRN) were reviewed, totalizing 77 cases. Immunohistochemical analysis for GLUT-1 showed that only 26 (33.8%) of the specimens were true infantile hemangiomas (IHs). The 51 (66.2%%) GLUT-1 negative specimens were then reclassified as pyogenic granulomas (PGs) and vascular malformations (VMs) from their histopathologic characteristics,totalizing 26 (33.8%) cases of IHs, 20 (26.0%) of PGs and 31 (40.2) cases of oral VMs. The cases analyzed by the marker Ki-67 showed different median IH (13,85), PG (33,70) and VM (4.55) with statistically significant differences between them (p <0.001). In relation to the protein Bcl-2, the groups also showed different median of the established scores IH (1.00), PG (1.50), VMs (0.0) demonstrating statistically significant differences between them (p<0,001). No statistically significant correlation between the indexes of positivity for Ki-67 and the scores of immunoexpression of Bcl-2 were observed in any group. Thus, we can conclude that it is necessary a careful and parameterized review of cases of vascular anomalies making use of auxiliary tools such as GLUT-1, since the histopathological findings alone, sometimes, are not sufficient to differentiate some anomalies. Furthermore, analysis of the expressions of markers involved in the levels of proliferation of lesions is important for a better understanding of its biological behavior aspect

Estudo da expressão imuno-histoquímica das proteínas MMP-9, MMP-13 e TIMP-1 em ameloblastomas e tumores odontogênicos ceratocistos

Ameloblastomas and keratocystic odontogenic tumors (KOT) represent odontogenic lesions that, despite their benign nature, are distinguished by a distinct biological behavior, characterized by locally aggressive growth and recurrent episodes. The gnathic bone resorption caused by the growth of these lesions is a key to the expansion of the same, both being mediated by osteoclastic cells like enzymatic activity of various matrix metalloproteinases (MMPs) factor. The expression of stimulatory factors and inhibitors of bone resorption has been correlated with the development of these lesions, with emphasis to some MMPs such as collagenases and gelatinases and tissue inhibitors of metalloproteinases (TIMPs), among others. Based on the premise that stimulatory and inhibitory factors of osteolytic processes can be decisive for the growth rate of intraosseous odontogenic lesions, this experiment evaluated the immunoreactivity of MMP-9, -13 and TIMP-1 protein in the epithelium and mesenchyme of ameloblastoma and the KOT specimens, by a quantitative analysis of the immunoreactivity cells. Statistical analysis was performed using the Mann-Whitney and Wilcoxon tests with a significance level set at 5 %. Immunohistochemical expression of MMP-9, -13 and TIMP-1 was observed in 100% of cases both in the epithelium and in mesenchyme. The immunoreactivity in the epithelium of KOT and ameloblastomas revealed a predominance of score 3 for MMP-9 (p=0.382) and MMP-13 (p=0.069) and no statistically significance for TIMP-1, the latter being significantly higher immunoreactivity in ameloblastomas. In the mesenchyme, there was a higher score immunoreactivity of MMP-13 (p=0.031) in ameloblastomas in relation to KOT, whereas for MMP-9 and TIMP-1 no statistically significant difference (p=0.403 was observed, p=1.000). The calculation of the ratio of scores revealed expression of proteins in general, similarity of the lesions, a significant predominance of equal expression of TIMP-1 and MMP-9 was observed only in the epithelium of ameloblastoma. The marked immunostaining of MMP-9 , MMP-13 and TIMP-1 in epithelium and mesenchyme of the lesion indicate that these proteins involved in ECM remodeling required for tumor progression, however, specific differences in the expression of some of these proteins, are not sufficient to suggest differences in the biological behavior of ameloblastomas and KOTs

Alterações nos genes da E-caderina e β-catenina em adenoma pleomórfico e carcinoma adenóide cístico: estudo molecular e imuno-histoquímico

Pleomorphic adenoma and adenoid cystic carcinoma represent a benign and malignant salivary gland neoplasm, respectively, that shares the same histological origin, however with distinct biological behavior. The aim of the present study was identify the -160 C/A polymorphism in the gene CDH1, mutational analysis of CTNNB1 gene and evaluation the expression of the E-cadherin and β-catenin in pleomorphic adenomas and adenoid cystic carcinomas. Furthermore, it was proposed correlate the immunochemistry staining patterns with the polymorphism and mutations. Twenty-four pleomorphic adenomas and 24 adenoid cystic carcinomas were retrieved. The polymorphism analysis was performed by restriction fragment length polymorphism (RFLP), using the restriction enzymes HphI or AflIII and the mutational screening was performed by PCR-single strand conformational polymorphism (PCR-SSCP). The immunohistochemical analysis was taken by the counting of cells, recorded as the Hscore index, and considering the presence or absence, intensity, distribution and localization of proteins expression. Comparing the two neoplasms, the results demonstrated statistically significant difference for the E-cadherin and β-catenin expression, with pleomorphic adenoma presenting weaker immunostaining. Was observed statistical correlation between E-cadherin and β-catenin expression. CDH1 heterozigotic polymorphism was seen in two cases and 13 cases displayed abnormal mobility electrophoretic shifts, suggesting CTNNB1 gene mutation. The immunohistochemical expression was not statistically correlated with the polymorphism or suggested mutations. In conclusion this study supports that the E-cadherin/β-catenin complex immunohistochemical expression might be related with the myoepithelial component amount and differentiation neither the tumor biological behavior. The cases that showed E-cadherin gene polymorphism presented reduced protein expression and, moreover, CTNNB1 suggested mutations seem not influence in the β-catenin protein expression

Estudo clínico-patológico do carcinoma epidermóide de língua e imunoistoquímico das proteínas BMP-2, BMPR-IA, BMPR-II e endoglina

Bone morphogenetic proteins (BMPs) are cytokines involved in proliferation and angiogenesis of many kind of human cancer. The present study analyzed the immunohistochemical expression of BMP-2, BMPR-II, BMPR-IA and endoglin (CD105) and their relationship with the biological behavior and local angiogenesis in tongue oral squamous cells carcinoma (SCC). The sample consisted of 25 cases of tongue SCC without metastasis, 25 tongue SCC with metastasis and 25 cases of Inflamatory Fibrous Hyperplasia (IFH).The histological grade of malignancy proposed by Bryne (1998), adapted by Miranda (2002) was used to classify all tongue SCC cases. Score 0 was attributed to absent-weak immunoexpression and score 1 for strong immunostaning and pattern of distribution was focal or diffuse. Microvessel counts (MVC) was established for CD105. Most of the patients with tongue SCC was male. The principal age in tongue SCC without metastasis was over 65 years and in tongue SCC with metastasis was between 45-65 years. There were predominance of stage II in TNM and in the specimens with high-grade, independent of studied group. For BMP-2, 56% of tongue SCC without metastasis and 72% tongue SCC with metastasis exhibited score 1 while the IFH showed secore 0 in 72% of the cases, with statistical association (p=0,007). Considering the BMPR-II, 52% of tongue SCC without metastasis exhibited score 0; 56% tongue SCC with metastasis and 60% IFH showed score 1. The majority cases of BMPR-IA demonstrated score 1 and 100% of CD105 exhibited strong immunoexpression in tongue SCC. Regarding the pattern distribution, it was noted a tendency to diffuse pattern for the proteins in all groups. The means of MVC were similar in tongue SCC without metastasis (32,91) and in tongue SCC with metastasis (32,05), however existed statistical difference with IFH (p<0,001). There was statistical association of BMP-2 expression with BMPR-II (p=0,008), BMPR-IA (p=0,006) and CD105 (p=0,046). An association between TNM and BMP-2 immunoexpression and their receptors was not detected, nevertheless this association was found with MVC (p=0,047) whose averages were higher for the stages II (35,97) e IV (35,69). No association between histological grading and these proteins was observed. This study suggests that the superexpression of BMP-2 signaling pathways acts on cell proliferation in tongue SCC and can be implicated with more invasive potential. Additionaly, the CD105 is a potent biological marker of neovascularization in this neoplasm and their association with BMP-2 and BMPR-IA receptor, showed that this type of cancer in BMP-2 is presented as pro-angiogenic in the metastatic process

Avaliação imuno-histoquímica das galectinas-1, -3, -4 e -7 em carcinoma epidermóide de língua.

Several studies are carried out with aim to establish parameters to determine biologic behavior of oral squamous cell carcinoma, in order this neoplasm presents high rates of morbidity and mortality. The purpose of present research was to performe a clinic, morphologic and immunohistochemical analysis by the expression of galectins 1, 3, 4 and 7 in 65 cases of tongue squamous cell carcinoma, correlating this expression with clinics (outcome of the disease, metastasis and clinical staging) and morphologic parameters (malignancy histologic gradation system). The clinical and morphologic parameters analysed and expression of galectins 1, 3, 4 and 7 were submitted to statistical analysis (Qui2 test), observing that can be utilized as indicators of the biological behavior of the tongue squamous cell carcinoma. The galectin 1 was expressed in 87,7% of cases studied and it exhibit statistically significant correlation with metastasis (p=0,033) and clinical staging (p=0,016), it is located mostly in the citoplasm of the stomal cells. The immunoexpression of galectin 3 in 87,7% of cases was correlated with the presence of metastasis (p=0,033) and malignancy histological gradation system (p=0,031), observed, mostly of cases, in tongue squamous cell carcinoma of malignancy high grading. The galectin 4 showed no statistical significance to any of the parameters evaluated. The expression of galectin 7 in 73,8% of cases showed statistically significant correlation with the malignancy histologic grading (p=0,005), which is marking exclusively found in neoplastic epithelial cells, in the mostly of cases, it is found in cytoplasm and membrane (50%). The expressive immunopositivy of the galectins 1, 3 and 7, observed in this research, leads us to suggest a broad participation of these proteins in oral carcinogenesis, and its possible use as markers of biological behavior and tumor progression in cases of squamous cell carcinoma of the tongue

Exprassão imuno-histoquímica dos fatores de reabsorção óssea em lesões centrais e periféricas de células gigantes

The Giant Cell Lesions, both the Central Giant Cells Lesions (CGCL) as the Peripheral Giant Cells Lesions (PGCL), correspond to a group of oral lesions that are histologically similar entities; however they show a variable clinical behaviour. The purpose of this study was to compare the immunohistochemical expression of bone resorption factors RANK (Receptor Activator of Nuclear Factor kappa B), RANKL (Receptor Activator of Nuclear Factor kappa B Ligand) and OPG (Osteoprotegerin) between CGCL and PGCL. Additionally, these bone resorption factors were examined in terms of aggressiveness of these lesions. The sample consisted of 61 cases, 30 cases of PGCL and 31 CGCL (16 non-aggressive and 15 aggressive). The analysis was performed by quantification of mononuclear cells (MO) and giant multinucleated cells (CG) immunopositive to anti-RANK, anti-RANKL and anti-OPG antibodies in 10 fields. Moreover, according to the proportion between the amount of cells positive for RANKL and OPG, the cases were categorized into: RANKL>OPG, OPG>RANKL e RANKL=OPG. CGCL showed a higher amount of MO (p=0.002) and total cells (p=0.003) both positives to RANKL compared with the PGCL. Additionally, the CGCL revealed a significant association with the ratio of RANKL>OPG (p=0.001). Analysis of the bone resorption factors revealed no significant differences between aggressive and non-aggressive CGCL (p>0.05). It was observed a positive correlation between the markers themselves, and a negative correlation between lesion size and quantity of OPG positive MO cells (p=0,004) and total cells (p=0,009). Through these results, we suggest that the greatest CGCL resorptive potential compared to the PGCL, may have occurred to the high expression of RANKL. Furthermore differences in the biological behavior of aggressive and non-aggressive CGCL appear to be related to the expression of these bone resorption factors

Estudo da imunoexpressão de RANKL e OPG, do índice angiogênico (CD34) e da presença de miofibroblastos (α-SMA) em ceratocistos odontogênicos isolados e associados à síndrome de Gorlin

The odontogenic keratocysts are distinguished from other odontogenic cystic lesions by their potentially aggressive clinical behavior and association, in some cases, with Gorlin syndrome. Studies have suggested that syndrome keratocysts, in comparison with sporadic lesions, have higher growth and infiltration capacity and higher recurrence tendency. The aim of this study was to analyze, by means of immunohistochemistry, the expressions of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), the angiogenic index (CD34) and the presence of myofibroblasts (α-SMA) in primary and recurrent sporadic keratocysts and in keratocysts associated with Gorlin syndrome. The sample was composed by 30 sporadic keratocysts (22 primary and 8 recurrent) and 22 syndrome keratocysts. In the epithelium and in the fibrous capsule of the lesions, the immunoexpression of RANKL and OPG was evaluated by determination of the percentage of positive cells, according to the following scores: 0 (less than 10% of positive cells), 1 (11% - 50% of positive cells), 2 (51% - 75% of positive cells) and 3 (more than 76% of positive cells). In addition, cases were classified according to the RANKL score/ OPG score ratio, as follows: RANKL > OPG, RANKL < OPG, and RANKL = OPG. The angiogenic index was analyzed by counting the microvessels immunoreactive to anti-CD34 antibody in 5 fields (200). The analysis of myofibroblasts was performed by counting the cells immunoreactive to anti-α-SMA antibody in 10 fields (400). The analysis of the expressions of RANKL and OPG in the epithelial lining and in the fibrous capsule did not reveal significant differences between groups (p > 0.05). Regarding the RANKL/ OPG ratio in the epithelial lining, most sporadic primary (54.5%) and syndrome lesions (59.1%) showed RANKL < OPG ratio and RANKL = OPG ratio, respectively (p > 0.05). With respect to the RANKL/ OPG ratio in the fibrous capsule, the majority of sporadic primary (81.8%) and sporadic recurrent lesions (75.0%) and most syndrome lesions (45.5%) showed RANKL = OPG ratio (p > 0.05). The mean number of microvessels was 69.2 in sporadic primary lesions, 67.6 in recurrent lesions, and 71.6 in syndrome lesions, with no significant differences between groups (p > 0.05). The mean number of myofibroblasts was 34.4 in sporadic primary lesions, 29.3 in recurrent lesions, and 33.7 in syndrome lesions, with no significant differences between groups (p > 0.05). In conclusion, the results of the present study suggest that the differences in the biological behavior between sporadic keratocysts and keratocysts associated with Gorlin syndrome may not be related to the expressions of RANKL and OPG, the RANKL/ OPG ratio, the angiogenic index or the number of myofibroblasts in these lesions

Estudo da expressão imuno-histoquímica das MMPs -2, -7, -9 e -26 e TIMPs -1 e -2 em adenomas pleomórficos e carcinomas adenóides císticos de glândulas salivares menores

The balance between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) has been related to various physiological and pathological processes, including salivary gland morphogenesis and tumor invasion and metastasis processes. Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) respectively represent benign and malignant neoplasias of salivary glands. Although they share the same cell origin, they present distinct biological behavior. The aim of this study was to compare the immunohistochemical expression of MMPs -2, -7, -9 and -26, and of TIMPs -1 and -2, in cases of PA and ACC of minor salivary glands. Twenty cases of PA and twenty cases of ACC were assessed according to the presence, intensity and location of MMPs and TIMPs in the tumor parenchyma. Most of the PAs and ACCs presented a high expression of MMP -2, -7, -9 and -26 and of TIMP -1 and -2, predominantly located in tumor cells. There was no significant difference in the expression of MMPs -2 (p=0.359), -7 (p=0.081) and -26 (p=0.553), as well as of TIMPs -1 (p=0.657) and -2 (p=0.248), between the parenchyma of PAs and ACCs. However, MMP-9 showed a significant difference of expression between the two tumors, with the ACC showing more intense marking for this gelatinase (p=0.041). The strong expression of MMP-9 observed in the parenchyma suggests that this gelatinase may play an important role in the biological behavior of these tumors. On the other hand, although there was no significant difference between the marking of MMP -2, 7 and 26 in the studied tumors, the data, when analyzed as a whole, suggest that these proteases may take part in the process of tissue remodeling in both tumors, but do not present a direct relation with the pattern of aggressiveness of ACC. Nonetheless, matrilisins may indirectly influence the behavior of this tumor due to their capacity of activating MMP-9, strongly expressed in the parenchyma of ACC

Avaliação da expressão imuno-histoquímica de marcadores de hipóxia em carcinoma epidermóide de língua

The tumor hypoxia modulates a series of genetic changes related to adaptive development, invasion and metastasis of various human cancers, among which squamous cell carcinoma of the tongue (SCCT). The objective of this study was to analyze clinical, morphological and immunohistochemical expression by HIF-1α, GLUT-1 and CA-IX in 57 cases of CEL and correlated this expression to clinical parameters and morphological. After a descriptive analysis of data on gender, age, race, and habits of patients, it was found that the results were consistent with the literature. The clinical and morphological parameters analyzed and the expression of these markers of hypoxia were subjected to statistical analysis (Qui2 test), verifying that they can be used as indicators of the biological behavior of CEL. Among the results of this study, we observed that the intensity of expression for HIF-1α, in most cases located in the cytoplasm and nucleus, statistically correlated with clinical staging (p = 0.011) and histological grading (p = 0.002). As for the relationship between the distribution of labeling for HIF-1α and metastasis, the chi-square (Qui2) showed that there was statistically significant differences between the groups (p = 0.040). 75.8% of the sample who had metastases, there was the predominance of diffuse marking. The immunoexpression cytoplasmic/membrane GLUT-1 showed a statistically significant correlation with the clinical stage (p = 0.002) and histological grading (p = 0.000). Concerning the location of markings for GLUT-1 tumor on the island, there was a predominance of peripheral marking specimens in most low-grade (78.6%). In the sample of high-grade, prevailed the location center/periphery (55.8%). According to the chi-square (Qui2), the location on the island of the tumor (p = 0.025) showed statistically significant difference in histological grading. The immunoreactivity of CA-IX, in most cases located in the membrane and cytoplasm, exhibited a statistically significant correlation with histological grading (p = 0.005). Based on these results, we can conclude a broad participation of these markers of hypoxia in oral carcinogenesis and its possible use as markers of biological behavior and tumor progression in CEL

Expressão imuno-histoquímica da e-caderina e da ß-catenina em carcinoma epidermóide oral com e sem metástase nodal

The adhesion molecules E-cadherin and β-catenin have been studied as possible markers to distinguish carcinomas with and without metastatic potential. The objective of this research was to study the imunohistochemistry expression of the E-cadherin and β-catenin in oral squamous cell carcinoma (OSCC), aiming to contribute for the better understanding of the biological behavior of this lesion. The sample consisted of 30 cases of OSCC, being 15 of tongue and 15 of lower lip. The profile and intensity of labeling and semi quantitative analysis of the percentage of immunopositive tumoral cells in membrane for E-cadherin and β-catenin had been related with the anatomical localization of the lesion, the presence or not of nodal metastasis and the histological grade of malignancy in the invasive front area of the tumor. It was registered the presence or not of cytoplasmic and nuclear labeling of the β-catenin. The results had been submitted to the statistical analysis, being used the Mann-Whitney Test, the Fisher Test and the Spearman Correlation Coefficient (α=0, 05). The results showed that the expression in membrane for E-cadherin and β-catenin was, predominantly, the heterogeneous profile in the lower lip and tongue carcinomas, as well as in the cases with and without nodal metastasis. It was not observed significant statistical difference between expression profile and amount of immunopositive cells for E-cadherin, β-catenin and the anatomical localization of the lesion and for the presence or not of nodal metastasis. However, there was significant difference of the reduced expression of these proteins with the high score of malignancy. It was verified that the expression of the β-catenin in cytoplasm was present in 22 (73.33%) of the 30 analyzed cases, and 6 cases (20%) showed nuclear expression. The statistical analysis detected significant association between the expression of the β-catenin in the cytoplasm with the histological grade of malignancy, being this molecule more frequently present in the cytoplasm in the cases of high score of malignancy. It was concluded that the reduced immunoexpression of these proteins in membrane can be related with the lowest cellular differentiation, as well as with the pattern of invasion in nests and isolated cells, demonstrated in the cases of OSCC with high histological grade of malignancy

Expressão imuno-histoquímica das integrinas α2ß1, α3ß, e α5ß1, em carcinoma epidermóide de lábio inferior e língua

The unpredictable biologic behavior of the oral squamous cells carcinoma has determined extensive research on the evolution of such tumor. Due to the existing relation between the outer cell matrix and the tumor cells, the integrins have been used as markers in the predictive study of the cell behavior. This study aims to analyze immunohistochemically the expression of the integrin α2β1, α3β1, and α5β1 connections for the collagen, the laminin and the fibronectin respectively in 15 cases of squamous cells carcinoma from the lower lip and 15 from the tongue, with different scores of malignance grading. A predominantly diffuse, cytoplasm and granular immunological marking was observed in the majority of the analyzed cases. According to the marking intensity, integrin α2β1 appeared positive in 80% of the lip and in 93,3% of the tongue cases. The immunological reactivity of integrin α3β1 was classified as positive in 60% of both the tongue and lip cases. For this integrin, 20% and 33.3% of the tongue and lip cases, respectively, were negative. In relation to integrin α5β1 the intensity was classified as positive in 53,3% of the cases and strongly positive in 46,7% of those located in the lip. In the tongue carcinomas, the intensity was positive in 46,7% of the cases and strongly positive in 53,3%. The statistic analysis did not show any significant differences or correlation of expression between these integrins nor between the anatomical sites or between different scores of malignancy grading. The expressive immunological marking of the integrins, α2β1, α3β1, and α5β1 in the studied cases of squamous cell carcinomas leads us to think of a great participation of these proteins in oral carcinogenesis; however, our results do not allow us to correlate its expression as an indicator of variations in the biological behavior of this neoplasia

Expressão imuno-histoquímica das integrinas a2ß1, a3ß1 e a5ß1 em adenoma pleomórfico de glândula salivar menor e maior e carcinoma adenóide cístico

Pleomorphic adenoma and adenoid cystic carcinoma (ACC) consist benign and malignant neoplasm from salivary gland, respectively. These neoplasms share some characteristics, such as cellular origin and considerable production of extracellular matrix, however, with distinct biological behavior. The aim of the present study was to compare the expression of D2E1, D3E1 e D5E1 integrins in pleomorphic adenoma from minor and major salivary glands and ACCs. Furthermore, it was investigated possible differences in the expression of these integrins according to histological subtypes of ACC. Fourteen cases of pleomorphic adenoma from major salivary gland, fourteen cases from minor salivary gland and ten cases of ACC were selected. It was taken into consideration the presence or absence, localization and intensity of integrin immunoexpression. The cases of pleomorphic adenoma were grouped in order to compare the expression between the distinct neoplasms. It was observed a highly significant difference (p<0,0001) in relation to D2E1 integrin between the neoplasms since pleomorphic adenoma showed a pronounced immunostaining. It was not possible to perform statistical tests considering the D2E1 integrin expression; nevertheless, it could be observed a tendency of higher staining in pleomorphic adenoma. For comparative reasons the cases ACCs were divided in two groups: solid and tubular/cribriform. It was not detected significant differences in regard to D2E1 integrin; and statistical analysis could not be realized in relation to D3E1 and D5E integrin expression. However, it was also verified a tendency of absence or reduced expression in the solid subtype. It can be concluded that the reduced D2E1 integrin expression observed in CACs may be related to a lesser degree of cell differentiation in this neoplasm and the reduced D5E1 integrin expression can be associated with aggressive biological behavior. Moreover, the absence and/or reduced expression of the studied integrins in solid ACC suggests a role in pathogenesis and more aggressive biological behavior of this histological subtype

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