Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Interconverting flavanone glucosides and other phenolic compounds in Lippia salviaefolia Cham. ethanol extracts

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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

Carcinoma epidermóide de língua :correlação clínica, histológica e imuno-histoquímica

Oral squamous cell carcinoma is the most common malignant neoplasm in oral cavity. Several studies have been carried out to establish biologic behaviour criteria of this neoplasm. Thus, the purpose of this experiment was to performe a clinic, morphologic and immunohistochemical analysis, by the expression of cytokeratins 7, 10, 13, 14, 16 and 19 in 30 cases of tongue squamous cell carcinoma from the files of Dr. Luiz Antônio Hospital (Natal-RN). It was verifeid of the immunoexpression the correlation clinic estadiament and histologic gradation system proposed by Bryne (1998), in order to investigate the use of these intermediate filaments as an indicator of tumour progression. Data was collected from the patients file and it was observed that information regarding sex, age and race was resemble to the literature. Data obtained from disease evolution, clinic estadiament, metastasis and expression of cytokeratins 7, 10, 13, 14, 16 and 19 was submited to statistical analysis (Test K2), which showed that only the histologic gradation didn t demonstrated significant correlation to the clinic variables. The expression the cytokeratins presented variation in the analysed tumours. CK 10 expression showed significant correlation to metastasis, and the presence of CK 16 was related to disease evolution (obit/remission) and also with the T3 and T4 of TNM. These results evidenced that metastasis and TNM showed a good efficacy as a prognostic indicator. The histologic gradation proposed by Bryne (1998) didn t reflect the biologic behaviour of the studied tongue squamous cell carcinoma, and the analysis of some intermediate filaments of cytokeratins seems to reflect the biologic behaviour and agressivity of some oral squamous cell carcinoma

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

Avaliação clínica da saúde bucal de crianças com neoplasias malignas atendidas no Hospital Infantil Varela Santiago em Natal-RN

The childhood cancer is characterized by a predominance of hematogenic and lymphatic system neoplasm, although a fTequency of the central nervous system tumors and sarcomas are widely common. Particularities of many childhood cancers and the adverses effect of the antineoplastic agents can change radically the oral environrnent and predisposes to the risk of oral complications. This study assessment clinically the oral health of 40 children on treatment for different types of malignant neoplasm with age range of O to 1S years old (Group I) and compared to 38 nonnal children in the same age range (Group lI). The results shown that nonnal patients had a gingival bleeding index (GBI) and caries experience minar than patients of Group lI, the visivel plaque index (VPI) was lightly higher in patients of Group 1. There was not difference statistically significant in the variables. Sixteen patients of Group I developed together 61 oral complications with predominance of mucositis, followed by spontaneous oral bleeding, candidiasis and xerostomy, that complication were most commons in patients with systemic neoplasm. Its was concluded that patients submitted to antineoplastic therapy with poor oral health had a higher risk to develop oral complications

Estudo da imunoexpressão dos transportadores de glicose 1 e 3 em carcinomas epidermóides de lábio inferior e sua relação com parâmetros clínico-patológicos

The Epidermoid Carcinoma (EC) is the most common lesions located in the region of the head and neck and, despite advances in treatment modalities, the prognosis is still poor. The malignant cells show an increase in glucose uptake, process mediated by glucose transporters (GLUTs). Increased expression of GLUT 1 and GLUT 3 is related to the aggressive behavior of this lesion. The aim of this study was to evaluate, through immunohistochemistry, the expression of GLUTs 1 and 3 in EC of the lower lip. The sample consisted of 40 cases of EC of the lower lip, of which 20 had regional lymph node metastasis and the remaining 20 with absence of metastasis. The percentages of immunostained cells in front of tumor invasion and in the center of tumor were evaluated. These results were related to the presence and absence of lymph node metastasis, TNM classification and histological grading. The percentage of cytoplasmic/membranous expression of GLUT 1 ranged from 77.35% to 100%, while for GLUT 3 this value ranged from 0.79% to 100%. As for nuclear staining for GLUT 1, this percentage ranged from 0 to 0.42%, however. GLUT 3 showed only one case with nuclear staining. Despite the significant expression of tumor cells related to the proteins studied, we observed no statistically significant relationship between the variables and the antibodies analyzed, regardless of the region evaluated. However, there was a moderate positive correlation between cytoplasmic/membranous immunoexpressions of GLUT 1 in invasion front and in the tumor center (r = 0.679, p <0.001). Similarly, moderate positive correlation was found between the nuclear immunoexpressions of GLUT 1 in the invasion front and in the tumor center (r = 0.547, p <0.001). For GLUT 3, was also observed a moderate statistically significant positive correlation between cytoplasmic/membranous expression in tumor invasion front and in tumor center (r = 0.589, p <0.001). We also observed that the immunoreactivity for GLUT 1 was higher than GLUT 3 expression in invasion front (p <0.001) and tumor center (p <0.001). From these results, this study suggests that tumor hypoxia is a remarkable characteristic of the EC of the lower lip and GLUT 1 may be primarily responsible for glucose uptake into the interior of the malignant cells

Valor prognóstico de células TCD8+ E natural killer em carcinoma epidermóide oral e orofaringeano tratado com radioterapia e quimioterapia

The most common malignant neoplasm of the oral cavity and oropharynx are squamous cell carcinoma. Injuries to the same stage and subjected to the same treatment protocol have sometimes different evolutionary courses. The scope of this study was to investigate, through a retrospective cohort, associations between the number of CD8 + T cells and natural killer, identified immunohistochemically in the inflammatory infiltrate in a series of cases of oral squamous cell carcinoma and orofaringeano, and the level of tumor response to radiotherapy and chemotherapy, overall survival and relapse-free survival of patients. We identified 54 patients with unresectable disease were treated exclusively with radiotherapy and chemotherapy. The median follow-up was 22 months. The sample was characterized by the predominance of male subjects, median age 60 years, all were smokers. The most frequent site was the tongue and 81.5% were in stage IV. Patients with disease in the oral cavity had a worse response to treatment (p = 0.006), worse relapse-free survival (p = 0.007), worse overall survival (p = 0.007). The advanced T stage was shown a negative prognostic factor (p= 0.006) for the clinical treatment response made. Immunohistochemistry was performed to select CD8 + cells (anti-CD8) and NK cells (anti-CD57). Lymphocytes positive and negative markings were counted using the program ImageJ ®. Two groups were created for each marking evaluated: Group I patients with more than 50% cells positive, Group II: less than 50% of labeled cells. For CD8 + cells detected in 38 (70.3%) of Group I were CD8 + and 16 (29.7%) Group II CD8 +. For NK cells, 26 (48.15%) Group I NK and 28 (51.85%) Group II NK. Regarding the clinical response to treatment, we observed that 39% of patients achieved a complete response and 25.9% remained without recurrence at the end of follow-up. These results were better in Group I CD8 + (p = 0.2). Identified that 72.2% of patients progressed to death, this finding had no association with the immunohistochemical data. There was no statistically significant differences between the number of CD8 + and NK cells and the ability of tumor response to radiotherapy and chemotherapy, or with overall survival and relapse-free survival of patients. However, especially in relation to a learned response, we found that this group of patients with advanced disease have a low count of CD8 + T cells active. Believing in the role that the immune response plays in the local fight against neoplastic cells, however, our results do not support the use of quantitative analysis of CD8 + T cells and NK cells as a prognostic factors for oral squamous cell carcinoma and oropharynx

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

Estudo da influência de linfócitos tcd-8 e das células nk em casos de carcinoma epidermóide de lábio inferior sem metástase e com metástase e sua relação com a progressão da lesão

The presence of inflammatory cells within the tumor microenvironment plays a dual role that may contribute both to the progression and for inhibition of tumor growth. Recent studies suggest that the quality, not the quantity, of the inflammatory infiltrate is the most important determinant for prognosis. Therefore, TCD8 cells and natural killer cells are the main effector cells in combating cancer. The aim of this study was to assess, through the immunohistochemical study, the expression of TCD8 lymphocytes and NK cells in epidermoid carcinoma (EC) of the lower lip. The sample consisted of 32 specimens of EC of the lower lip, of which 16 had regional lymph node metastasis, and the 16 remaining, free of metastases. The total number of positive cells at the front of invasion were evaluated quantitatively and the results were related to clinical TNM staging, histological grade of malignancy and prognostic factors. It was observed for the group with metastasis, prevalence of stages III and IV (p<0.0001). Most patients with metastasis, had a high grade of malignancy (p=0.006). Most cases classified as high grade of malignancy had stages III and IV (p=0.032). Of the total sample, there were three cases of recurrence and five with death, however these variables were not statistically significant when associated with clinicopathological parameters. The immunostaining of CD8 and CD57, respectively, showed no statistically significant association with any of the clinicopathological parameters studied, metastasis (p=0.346, p=0.622), TNM classification (p=0.146, p=0.576), histological grade of malignancy (p=0.936, p=936), recurrence (p=0.075, p=0.075) and death (p=0.897, p=0.856). Believing in the function of the immunological system against malignant cells, it is concluded that the TD8 lymphocytes and NK cells, would be acting in the control of the progression of malignant neoplasms, but not in isolated manner

Expressão imuno-histoquimica da cicloxigenase-2 e p53 em cancinoma epidermóide oral

Squamous cell carcinoma is the most common malignant neoplasm in the oral cavity, accounting for more than 90% of all malignancies in this location. Cyclooxygenases (COX s) are key enzymes on arachidonic acid metabolism and prostaglandin synthesis, being expressed basically in two forms: the constitutive (COX-1) and the inducible (COX-2). Increased levels on the expression of COX-2 have been implicated in the pathogenesis tumor progression of various forms of human cancer, including oral squamous cell carcinoma, some of what suggesting a possible interaction between COX-2 and the protein expressed by the tumor suppressor gene p53, mutated in more than 50% of all human cancers. The mean of the present research consisted in analyze the correlation between the expression of COX-2 and p53, at the protein level, as well as evaluate the difference on the expression of these two proteins with the histological grading of malignancy. 34 cases of oral squamous cell carcinoma were selected and graded according to the histological grading system proposed by Bryne (1998) and the labeling indexes (LI s) for COX-2 and p53 evaluated using immunohistochemistry method. The results revealed that COX-2 was expressed in increased levels in most of the specimens, although there was no statistic significant correlation between LI s from COX-2 and p53 (p>0.05), and there were no statistical differences on the expression of these proteins between tumors of high and low grade of malignancy (p>0.05). Interestingly, the expression of COX-2 and p53 was detected in fragments of dysplastic oral epithelium adjacent to tumor areas, on basal and suprabasal layers. The absence of statistical correlation between the expression of COX-2 and p53 proteins do not rule ot the existence of a relation between them, were it may reflect the diversity of regulatory pathways between both, different direct and indirect inhibitory effects of COX-2 over p53, as well as the wide range of activation macheenisms for COX-2 and mutational status of the p53 gene Another conclusion point that the increased expression of COX-2 observed in oral squamous cell carcinomas suggest a role for this protein in the processes of pathogenesis and tumoral evolution of this malignant neoplasm

Avaliação da expressão da BMP -2/4 e BMPR-IA em Carcinoma Epidermóide Oral metastático e não metastático

The expression of bone morphogenetic proteins (BMPs) is altered in a variety of human canceres. The BMP-2/4 and BMPR-IA were recently shown to be overexpressed in high-risk premalignant and malignant lesions of oral epithelium. The present study analysed the expression of BMP-2/4 and BMPR-IA in Oral Squamous Cell Carcinoma (OSCC) such as their implications in disease prognostic using munohistochemistry. Ten cases of Oral Fibroepithelial Hiperplasia were selected as a control group. The experimental group included 16 cases of OSCC without metastases and 7 cases of OSCC metastatic. The presence or absence of nodal metastases was used as parameter to evaluated the disease prognostic. The results demonstrated weak immunoreactivity for BMP-2/4 and BMPR-IA in every case of the control group. In the cases of OSCC with metastases an overexpression of BMP-2/4 (71,4%) was observed while the BMPR-IA showed weak expression (85,7%). In the cases of OSCC without metastases BMP-2/4 (62,5%) and BMPR-IA showed strong immunostaining standing out an overexpression of the receptor in all the specimens. Observed statistical significance for correlation between the oral cancer prognostic and the staining intensity of the BMP-2/4 (p=0,002). There wasn t statistical significance for association between the staining intensity of the BMPR-IA and the disease prognostic (p<0,001). In conclusion, this findings suggest that the overexpression of BMP-2/4 associated with the loss of expression of the BMPR-IA in OSCC metastatic has prognostic relevance, as the loss of sensitivity to BMPs can be an indicative of metastases development in OSCC

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

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