Relação entre os critérios diagnósticos histológicos e a expressão imuno-histoquímica da P53 no carcinoma prostático

Introdução e Objetivo: o gene TP53 é o alvo isoladamente mais comum de mutação em tumores humanos. Está envolvido no bloqueio do ciclo celular, reparo ao DNA, diferenciação celular e apoptose, em resposta ao dano genético. O exame de imuno-histoquímica (IHQ) pode detectar o acúmulo da proteína p53 no núcleo celular, indicando mutação. Esta mutação tem sido associada a comportamento agressivo nos carcinomas prostáticos. O conhecimento das características histológicas deste carcinoma permite o estabelecimento de critérios diagnósticos anatomopatológicos e de graduações histológicas que visam a um melhor atendimento dos pacientes com a doença. O estudo da relação entre os achados de biologia molecular e as características histológicas desta neoplasia leva a um maior conhecimento de mecanismos que produzem as alterações morfológicas teciduais, auxiliando na identificação de novas variáveis promissoras na determinação do comportamento biológico da doença. Material e Método: foram examinadas amostras de 101 exames de biópsias por agulha da próstata, de setenta pacientes com carcinoma, através de lâminas coradas pelo HE, selecionados de 500 exames consecutivos. Obtiveram-se novos cortes dos mesmos blocos de parafina, sendo estes corados pela técnica de IHQ, utilizando o anticorpo monoclonal DO7 para p53, em 69 dos pacientes. Foram anotados, para estudo de associação, os achados morfológicos de carcinoma, o padrão da coloração IHQ para p53, a presença de invasão de nervos (IN) pelas colorações HE e de IHQ para proteína S100 e algumas características clínico-laboratoriais dos pacientes com carcinoma prostático. Resultados: dentre as formas de aferir a positividade IHQ da p53, a imunorreatividade em grupamento foi o padrão que melhor se correlacionou com os achados clínico-patológicos examinados: PSA sérico, escore de Gleason, quantidade de tumor na amostra (p<0,01) e presença de invasão de nervo. Dentre os critérios diagnósticos estudados, houve associação estatisticamente significativa da imunorreatividade em grupamento para p53 com as presenças de micronódulos de colágeno e mais de um nucléolo proeminente no mesmo núcleo de célula neoplásica. Quanto à IN, apenas quando a mesma foi identificada com a técnica de IHQ (proteína S100), houve associação estatisticamente significativa. Conclusão: o padrão de imunorreatividade em grupamento mostra-se superior aos demais quando comparado aos achados anatomopatológicos com valor preditivo em biópsias e com o valor do PSA sérico. A associação estatisticamente significativa entre a imunorreatividade em grupamento para p53 e a presença de IN detectada com a utilização da proteína S100 contrasta com a ausência de significância quando a IN é identificada na histologia convencional (HE). Estes achados recomendam novos estudos para verificar a utilidade da determinação IHQ da IN no prognóstico da doença e para identificar o mecanismo molecular de invasão de nervos de pequeno tamanho que não são facilmente identificados no HE. A presença da associação da positividade IHQ para p53 com micronódulos de colágeno igualmente recomenda novos estudos clínicos e moleculares para esclarecimento da relação deste achado histológico com o comportamento biológico do carcinoma prostático.

Expressão imuno-histoquímica metaloproteinase -1, -2 e -9 em ameloblastoma sólido e tumor odontogênico adematóide

Ameloblastoma and adenomatoid odontogenic tumor are odontogenic tumors arising from the odontogenic epithelium with distinct clinical behavior. In attempt to comprehend the interaction between the odontogenic tumor cells and the extracellular matrix, the present work evaluated and compared the immunohistochemical expression of the matrix metalloproteinases-1 (MMP-1), -2 (MMP-2) and -9 (MMP-9) in 20 cases of ameloblastoma and 10 adenomatoid odontogenic tumor. MMP-1 exhibited exuberant expression in the parenchyma and in the stroma of both studied tumors, while the MMP-2 showed varied expression with about of 80% and 60% of the neoplastic cells exhibiting positivity in the ameloblastoma and adenomatoid odontogenic tumor, respectively. With relation to the MMP-2 expression by the mesenchymal cells, it was observed that 65% of the ameloblastoma and 80% of the adenomatoid odontogenic tumor were positive. The immunoreactivity of MMP-9 was detected in all studied cases, although its expression had occurred predominantely in less than 50% of the parenchyma cells of the ameloblastoma, while in about of 60% of the adenomatoid odontogenic tumor more than 50% of cells were positive. The mesenchymal cells were positive to MMP-9 in 65% of the ameloblastoma and in 80% of the adenomatoid odontogenic tumor, respectively. Statistically significant difference was observed to the MMP-1 expression with relation to MMP-2 and MMP-9 in the ameloblastoma (p < 0.001). It was not possible to perform statistical analysis to the cases of adenomatoid odontogenic tumor, however there was a tendency toward a differential expression of the MMP-1 with relation to other studied MMPs. These results suggest that MMP-1, - 2 and -9 are implicated in the growth and progression of both tumors analyzed as well as the more pronounced participation of the stroma in the ameloblastoma could together to be related to the higher clinical aggressiveness

Expressão imuno-histoquímica dos marcadores angiogênicos CD105 (endoglina) e CD34 em hemangiomas e granulomas piogênicos orais

Angiogenesis, a fundamental mechanism in tumor development, is used for differential diagnosis and prognosis purposes in various neoplasias of the head and neck. This study proposes to assess angiogenic activity using immunohistochemical expression by anti-CD105 and anti-CD34 antibodies in 20 cases of hemangiomas and 20 cases of oral pyogenic granulomas, in addition to determining the usefulness of these markers as one of the differential diagnosis resources for these two oral lesions. The results showed no statistically significant difference between microvascular count (MVC) means determined by anti-CD105 (p = 0.803) and anti-CD34 (p = 0.279) antibodies. The mean number of vessels obtained by MVC in the oral hemangiomas immunostained by anti-CD105 and anti-CD34 was 18.75 and 59.72, respectively, whereas in the oral pyogenic granulomas, the mean number was 20.22 and 48.09 respectively. It was also shown that CD34 was more effective than CD105 in identifying blood vessels. However, it must be pointed out that the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this assay reinforces the role of angiogenic factors in the etiopathogenesis of hemangiomas and oral pyogenic granulomas, but the results showed that angiogenesis quantification cannot be used as a differential diagnosis parameter between the two lesions analyzed

Expressão Imuno-histoquímica da triptase em mastócitos nos Fibromas de Células Gigantes e Hiperplasias Fibrosas de Mucosa Oral

The giant cell fibroma is a benign neoplasm characterized by the presence of mono, bi or multinucleate cells, which can have a connection to the presence of mast cells. This research aims to analyze, descriptively and comparatively, the immunohystochemistry expression of the tryptase in mast cells of the giant cell f ibroma, f ibrous hyperplasia and samples of the normal oral mucosa. Thirty cases of giant cell fibroma, ten cases of fibrous hyperplasia and ten cases of normal oral mucosa were selected for the analysis of the immunohistochemistry expression, determination of the number of present mast cells, as well as their location and shape. It could be stated that there was a statistically signif icant difference (p<0,001) in relation to the quantity of mast cells among other samples analyzed where the giant cell f ibroma presented lesser quantity of mast cell and the hyperplasia showed higher concentration of this cellular type. Although the oral mucosa has presented a higher quantity of mast cells when compared to the giant cells fibroma, these were found in usual locations in the connective tissue in normal tissues. There could be noticed a statistically significant difference in relation to the number of non-granulated mast cells (p<0,001). On the areas of fibrosis, we could observe a statistically signif icant difference (p<0,006) among the samples. In relation to the present mast cells in perivascular location, no statistically signif icant difference was found. On the morphological analysis there was a predominance of oval mast cells. It was concluded that despite of the fact there was a lesser quantity of mast cells present in cases of giant cell f ibroma, they appeared to have a stronger relation to the present giant fibroblasts in this lesions, around 59,62%, being also evidenced a strong relation between these cells and the fibrosis areas in both cases of giant cell f ibroma and f ibrous hyperplasias and samples of normal oral mucosa, used as control group in our study, confirming, this way, the role of the mast cells as fibrinogenous inductor

Expressão imuno-histoquímica da calponina em glândula parótida de rato após obstrução do ducto excretor principal

Glandular atrophy is one of several alterations which can aflict the salivary glands, caused generally by obstructive lesions such as sialo1ithiasis, infections or compression by neoplastic processes arnong others. In this work, a morphological and immunohistochemical study was carried out in rat parotid glands, which were submitted to obstruction of the main excretory duct suffering atrophy at varied time intervals, with the aim of appraising the behavior of myoepithelial cells during the process of glandular atrophy. It was analized the immunohistochemical expression of calponin which detects myoepithelial cells in the parotids of 28 animaIs, which were divided into 7 groups, each one made up of 4 rats, afier the ductal ligature procedure, in the following time intervals: zero hour (control), 24 hours, 7, 15, 21, 30 and 60 days. Analysis of the immunohistochemicaI profile was carried through in which the calponin expression was veritied through its distribution pattem and numericaI index. All specimens exhibited positivity for calponin in myoepithelial cells which were distributed around the acini and the ductaI structures, a small number of positiveIy marked cells being detected in the controI group and in the 24-hour group when compared to subsequent ones, where it was perceived a Iarge increase in the number of positiveIy marked cens, mainly surrounding the ductiform structures which originated during the obstruction time. Upon application of statistical tests it was verified that the rise in the number the myoepithelial positive cells for calponin, when the control groups (zero hour) was compared to the 7, 15,21, 30 and 60-day groups afier obstruction, was statistica1ly significant. It was concluded then that the detected rise probably carne about due to an elevation in the rate of proliferation of the myoepitheliaI cells subsequent to the ductal obstruction, associated with a growing resistance of these cells to glandular atrophy.

Expressão imuno-histoquímica das proteínas MMP-9, VEGF e FVW em lesões centrais e periféricas de células gigantes

Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) of the jaws have a distinct clinical behavior, although they share histopathologic features. It is still unclear whether these clinical differences are supported by a distinct pattern of immunoexpression of markers for multinucleated giant cells (GC) and mononuclear cells (MC). The purpose of this study was to compare the immunohistochemical expression of VEGF, MMP-9 in CG and MC and measure the vascularization by vWF to check whether there are differences in expression of these biomarkers between CGCL and PGCL. Paraffin wax blocks of 20 cases of LCCG and 20 LPCG were retrieved. MMP-9 immunoreactivity was greater in the CM of PGCL compared to VEGF (p<0.05). VEGF expression was greater in the CM of CGCL compared to PGCL (p<0.05) and it was greater in the overall expression of CGCL compared to PGCL (p<0.05). Vascularity was quantified by microvascular counting (MVC). MVC was greater in the PGCL compared CGCL (p<0.05). MMP-9 showed a greater tendency of expression in CGCL, though was not significant (p>0.05). We tested correlation between the proteins studied in each group and found a significant negative correlation between VEGF and vWF in CGCL (p<0.05). These results suggest that there are differences in the expression of VEGF in CM and overall expression between the lesions, although no statistically significant difference in the overall expression of the MMP-9. Then, there was a trend in increased expression of MMP-9 and VEGF in CGCL, possibly by the involvement of both proteins in osteoclastogenesis. Additionally, the results of this study indicate a higher degree of vascularization in PGCL compared to CGCL, fact that can be directly linked to the reactive nature of the PGCL, where the inflammatory process with its rich angiogenesis contributes significantly to these findings.

Estudo comparativo da expressão imuno-histoquímica do ki-67 em carcinoma epidermóide de língua em pacientes jovens e idosos

The squamous cell carcinoma (SCC) is the most common malignant neoplasm of epithelial origin in oral cavity and present high capacity to invade adjacent structures. Traditionally, SCC has a predominance of 50 years male patients with long-time use of tobacco and alcohol, and the tongue is the most affected anatomic site. At present, there is an increasing incidence of SCC in patients below 40 years of age, who has been exposed or not to risk factors, mainly for tongue lesions. This study aims to analyze cell proliferation index using Ki-67 antigen in SCC of the tongue for two groups of different age range: until 40 years and older than 50 years. The first group was composed by 16 patients and the second one was composed by 20 patients. Clinicopathological features of the cases were also assessed. There was a male predominance in both groups. Tobacco and alcohol habits were common for patients until 40 years (72,2%), as well as for patients older than 50 years (52,9%). The first group had statistical association with the presence of regional metastases (p = 0,036) and with the most advanced stages of the disease (p = 0,012). Considering the histological malignancy grading, there was higher incidence (56,2%) of high malignancy grade tumors in the group of patients until 40 years old, but no statistical difference has found between groups and histologic malignancy grading. Regarding the immunohistochemical expression of Ki-67, there was no statistically significant difference between the antibody expression of the groups, as well as between other clinical and histopathological parameters. This study identified no significant difference regarding cell proliferation between the analyzed groups

Expressão Imuno-histoquímica das proteínas GLUT-1 e HIF-1α em lesões vasculares de mucosa oral

The correct histological diagnosis of vascular lesions in the oral mucosa is critical, especially in defining the treatment and prognosis, as some vascular lesions show spontaneous involution and others do not show such behavior. This study analyzed the expression immunohistochemistry of human glucose transporter protein (GLUT-1), in oral benign vascular tumors and to reclassify such lesions according to with his immunoexpression. In addition, we evaluated the immunohistochemical expression of hypoxia-inducible factor 1 alpha (HIF-1α), the main transcription factor involved in cellular adaptation to hypoxia. We analyzed 60 cases of benign oral vascular tumors: 30 cases with histological diagnosis of HEM and 30 cases of oral pyogenic granuloma (PG). The results of this research showed that of the 30 lesions initially classified as HEM, only 7 showed immuno-positivity for GLUT-1, remaining with the initial diagnosis. The remaining 23 were reclassified as vascular malformation (VM) (13 cases) and PG (10 cases). All cases in the sample with an initial diagnosis of PG were negative for GLUT-1, demonstrating the accuracy of histological diagnosis of these lesions. Concerning to the immunoexpression of HIF-1α, the Mann-Whitney test revealed a statistically significant difference between the cases of GP and MV (p = 0.002), where the median of GP (m=78) was higher than the MV (m=53). Based on these results, this study showed that a histological diagnosis alone is not always sufficient for the correct diagnosis of oral HEM and that HIF-1α participates in the pathogenesis of vascular lesions

Expressão imuno-histoquímica de IL-17, TGF-β1 e FOXP3 em ganulomas periapicais, cistos radiculares e cistos radiculares residuais

Periapical lesions are chronic inflammatory conditions of periradicular tissues considered direct consequences of infectious diseases resulting from pulp necrosis and subsequent progression to periapical region. The participation of the immune response and bone resorption in the formation of these lesions has been investigated, so that different cell types and cytokines have been identified as contributors to this process. In this perspective, this study aimed to evaluate the immunohistochemical expression of IL-17, TGF-β1 and FoxP3 in periapical granulomas (PGs), radicular cysts (RCs) and residual radicular cysts (RRCs), seeking a better understanding of the etiopathogenesis these periapicopatias. To this end, we selected 20 cases of GPs, 20 CRs and 10 RRCs to undergo morphological analysis and immunohistochemistry for biomarkers above, the latter being performed quantitatively using scores and average percentages of immunostaining for the analysis of IL-17 and TGF- β1, while for the FoxP3 were counted only the positive lymphocytes. The results showed statistically significant differences between TGF-β1 and FoxP3 imunoexpressions, in relation to the periapical lesions studied (p = 0.002, p <0.001, respectively) but not between IL-17 and these (p = 0.355). Furthermore, the analysis of lymphocytes FoxP3-positive revealed significant statistical differences in that refers to the intensity of inflammatory infiltrate (p = 0.003) and also regarding thickness of the epithelial lining (p = 0.009). Finally, it was observed in the case of PGs, strong positive correlation between the amount of FoxP3- positive lymphocytes and the immunohistochemical expression of TGF-β1 (r = 0.755, p<0.001), as well as moderate positive correlation between IL-17 and TGF-β1 imunoexpressions (r = 0.503, p = 0.024). Thus, we can conclude that interactions between Th17 and Treg cells seem to be established at the site of injury, suggesting the involvement of both pro-inflammatory and immunoregulatory cytokines in the pathogenesis of periapical lesions

Expressão imuno-histoquímica das proteínas IFN-γ e TGF-β1 em cistos radiculares e cistos dentígeros

Odontogenic cysts are pathologic cavities covered by odontogenic epithelium and filled by liquid, desquamated cells or other materials. The intraosseous lesions, such as radicular cyst and dentigerous cyst, present a potential of expansion capable of promoting the destruction of the surrounding osseous tissue. The mechanisms related to this process of expansion are the proliferation of cystic epithelium, the increase of the osmolarity of the cystic fluid and the synthesis of reabsorption factors such as IFN-γ and TGF-β1. The aim of this study was to evaluate and compare the immunohistochemical expression of IFN-γ and TGF-β1 between radicular cysts and dentigerous cysts in order to understand the role and behavior of these proteins in the expansion of these cysts. We selected 20 cases of radicular cyst and 20 cases of dentigerous cyst chosen from the files of UFRN s Laboratory of Oral Pathology. After analyzing the clinical data, the cases underwent the routine staining technique (HE) and immunohistochemistry for the appearance of IFN-γ and TGF-β1 in the epithelium and capsule of these cysts. The statistical analysis using the Mann-Whitney test revealed no statistically significant difference in immunoexpression of IFN-γ between the epithelium (p = 0.565) and capsules (p = 0.414) of radicular cysts and dentigerous cysts. Moreover, there was no statistically significant difference of immunoexpression of TGF-β1 between the epithelium (p = 0.620) and capsules (p = 0.056) of radicular cysts and dentigerous cysts. The Wilcoxon test revealed no statistically significant difference between IFN-γ and TGF-β1 imunoexpressions in the epithelium (p = 0.225) and capsules (p = 0.370) of radicular cysts. There was no statistically significant difference between IFN-γ and TGF-β1 imunoexpressions in the epithelium (p = 0.361) of dentigerous cysts. However, there was a statistically significant difference between IFN-γ and TGF-β1 immunoexpressions in the capsule (p = 0.001) of dentigerous cysts, being TGF-β1 the factor which presented the most significant immunoexpression. Given these results, we conclude that there was no difference in immunohistochemical expression of IFN-γ and TGF-β1 between radicular and dentigerous cysts and that TGF-β1 was more significant than the IFN-γ in the capsule of dentigerous cysts

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

Expressão imuno-histoquímica do cd8, foxp3, Tgf β, tnf α e nf-кb em displasias epiteliais e Carcinomas epidermóides orais

The Oral Epithelial Dysplasia (OED) is the lesion that precedes or co-exists with the Oral Squamous Cell Carcinoma (OSCC), presenting molecular and/or histological similar alterations. The divergences about the malignization potential of OEDs and the role of inflammation in this process make hard the early diagnosis and evaluation of OSCCs aggressiveness. Thus, it became the goal of this study to evaluate the role of inflammation in oral carcinogenesis and tumoral aggressiveness. For this purpose a morphological study was performed in 20 OED cases and 40 OSCC cases to detect the malignization potential of OEDs and the histologic malignancy grading (HMG) of OSCCs, analyzing superficial masses for dismorphism evaluation and the invasive front for evaluation of tumoral growing; and immunohistochemical, using anti-CD8, anti-FOXP3, anti-TGFβ, anti-TNFα and anti-NF-кB antibodies, comparing their with the types lesion, histological degree and intensity of the inflammatory infiltrate. The results were statistically significant for the parameters: cell maturity (p=0,0001), masses presence (p=0,038) and dismorphism (p=0,037), when associated to HMG. To compare the expression of the markers with the types lesion, a significantly higher expression of CD8 (p=0,001) and NF-кB (p=0,002) in the OED, and also a smaller expression of the epithelial TGFβ in the severe OEDs (p=0,011), without significant expression between OSCC degrees. By relating the expression of the studied markers with the inflammatory infiltrate intensity, a positive relation was observed with: inflammatory TNFα(p=0,003), epithelial TNFα and NF-кB (p=0,051 and p=0,004), in OEDs; and with CD8 (p=0,021) and TNFα (p=0,015) in conjunctive OSCCs; and a negative relation with epithelial TNFα (p=0,034) in OSCCs. No significant relation was found between FOXP3 with any of the studied variables. These findings lead to the conclusion that, the study of the invasive front is as important as the study of superficial masses for the evaluation of tumoral aggressiveness; the intensity of the inflammatory infiltrate has no use as a parameter for prognostic evaluation of OSCC in routine exams, but, the molecular events detected in this study may be necessary to give basis for determining the malignant potential in OEDs and aggressiveness in OSCCs

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 de COX-2, EMMPRIN, HIF-1α e GLUT-1 no tecido gengival normal e inflamado

The aim of this study was determine whether an association exists in the gum tissue between the expression of markers of tissue hypoxia (HIF-1α and GLUT-1) with a marker of inflammatory activity (COX-2) and a marker of collagen degradation (EMMPRIN). Was performed immunohistochemistry with antibodies specific for these markers on 60 samples of gingival tissue divided into two groups: gums (n = 26) and gingivitis (n = 34) and expression was analyzed in the epithelial tissue and connective tissue . The reactivity epithelial for COX-2 was observed in only two cases as the HIF-1α, GLUT-1 and EMMPRIN was strongly expressed in the epithelial basal layer and the immunostaining was gradually decreased as the cells away from this layer, and negative in the region suprabasal in most specimens. In connective tissue, and HIF-1α EMMPRIN were strongly positive for most cases analyzed as GLUT-1 was negative in most cases. Immunostaining for COX-2 showed an association with gingival inflammatory infiltrate. The expression of EMMPRIN, HIF-1α and GLUT-1 in normal gums confirms the physiological role of these markers, however there was no association with tissue inflammation. Given the findings we can conclude that the inflammatory changes installed in frames of chronic gingivitis may not be sufficient to activate the factors of hypoxia to levels that can be quantified by immunohistochemical analysis, in addition, the findings are not conclusive in relationship to involvement of EMMPRIN in the secretion of MMPs to degrade collagen in the frames of gingivitis. We suggest the use of technical analysis and quantification of RNA of EMMPRIN and MMPs in order to determine whether collagen degradation observed in gingivitis suffers or not, significant influence of EMMPRIN for secretion and activation of MMPs