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Study of expression of systems CXCR4-CXCL12/SDF-1, CCR7-CCL21 and Ki-67 in the oral squamous cell carcinoma and their association with clinicopathological factors,nodal metastases and survival / Estudo da imunoexpressÃo dos sistemas CXCR4-CXCL12/SDF-1, CCR7-CCL21 e Ki-67 no carcinoma de cÃlulas escamosas oral e sua associaÃÃo com indicadores clÃnicopatolÃgicos, metÃstase linfonodal e sobrevidaGalylÃia Menezes Cavalcante 16 July 2013 (has links)
Chemokines are responsible for the directed migration of leukocyte chemotactic cytokines, coordinating cell movement during inflammation and the transport of hematopoietic cells. In addition to leukocytes, chemokine receptors are also found in neoplastic cells and tumors associated with stromal cells. Among chemokines, and the CXCR4/CXCL12 CCR7/CCL21 systems have been shown the involvement of lymph node metastases or distant metastases in different cancers. Thus, aim of this study was to evaluate the expression of CXCR4, CXCL12, CCR7, CCL21 and Ki-67 in oral squamous cell carcinoma (SCC) and to correlate these markers with clinicopathological indicators, lymph node metastasis and survival. We conducted a survey of reports and paraffin blocks of excisional biopsies of patients with SCC treated at the Hospital Haroldo JuaÃaba (2001-2009). Data on anatomic location of the lesion, sex, age, patient survival, degree of histological differentiation of the tumor, tumor stage and presence or absence of lymph node metastasis, lymphovascular and perineural invasion, nuclear grade and depth of invasion were collected. For immunohistochemical analysis, followed by the technique of streptavidin-biotin-peroxidase using the anti-CXCR4, anti-CXCL12, anti-CCR7, anti-CCL21 and Ki-67 antibody. Histological sections were photomicrographed in 10 fields chosen randomly and measured for the number of labeled tumor cells and determined the percentage of each labeling antibody. The marking of CXCR4 was detected in the cytoplasm and nucleus, CXCL12, CCR7 and CCL21 were only cytoplasmic, their expression was observed in 18 (60%) 8 (22.66%) 16 (53.3%) and 3 (12%) cases, respectively. We found a significant positive association between lymphovascular invasion and immunostaining of CXCR4 (p = 0.007) and CCR7 (P = 0.01) and among these cases metastasis was present in 62.5% and 37.5%, respectively. When in combination with Ki67, we found a significant positive correlation between CXCR4 (p = 0.0086), CXCL12 (p = 0.036) and CCR7 (p = 0:04). Among patients CXCR4 + over 111 months, only 38.4% were alive (p = 0.845), whereas both patients CCR7 + (p = 0.398) as well as CXCR4 +, and CCR7 + (p = 0.441) after 62 months, everyone had already died. We conclude that these chemokines are associated with lymphovascular invasion and cell proliferation, perhaps favoring the development of metastasis and poor prognosis. / As quimiocinas sÃo citocinas quimiotÃticas responsÃveis pela migraÃÃo direcionada de leucÃcitos, coordenando o movimento celular durante a inflamaÃÃo e o transporte de cÃlulas hematopoiÃticas. AlÃm dos leucÃcitos, os receptores de quimiocinas tambÃm sÃo encontrados em cÃlulas neoplÃsicas e em tumores associados com cÃlulas estromais. Dentre as quimiocinas, os sistemas CXCR4/CXCL12 e CCR7/CCL21 tÃm sido demonstrado no envolvimento de metÃstases linfonodais ou à distÃncia em diferentes tipos de cÃncer. Dessa forma, foi objetivo desse trabalho avaliar a expressÃo de CXCR4, CXCL12, CCR7, CCL21 e Ki-67 em carcinoma de cÃlulas escamosas orais (CEC) e correlacionar estes marcadores com indicadores clÃnicopatolÃgicos, metÃstase linfonodal e sobrevida. Realizou-se um levantamento de laudos e blocos parafinados de biopsias excisionais de pacientes portadores de CEC tratados no Hospital Haroldo JuaÃaba (2001 a 2009). Foram coletados dados sobre localizaÃÃo anatÃmica da lesÃo, sexo, idade, sobrevida do paciente, grau de diferenciaÃÃo histopatolÃgica do tumor, estadiamento tumoral e presenÃa ou ausÃncia de metÃstase linfonodal, invasÃo linfovascular e perineural, grau nuclear e profundidade de invasÃo. Para reaÃÃo de imunohistoquÃmica, seguiu-se a tÃcnica da estreptavidina-biotina-peroxidase, utilizando os anticorpos anti-CXCR4, anti-CXCL12, anti-CCR7, anti-CCL21 e Ki-67. As secÃÃes histolÃgicas foram fotomicrografadas em 10 campos escolhidos aleatoriamente e quantificadas quanto ao nÃmero de cÃlulas tumorais marcadas e determinado o percentual de marcaÃÃo de cada anticorpo. A marcaÃÃo de CXCR4 foi detectada em citoplasma e nÃcleo, CXCL12, CCR7 e CCL21 tiveram marcaÃÃo apenas citoplasmÃtica, sendo observada suas expressÃes em 18 (60%), 8 (22,66%), 16 (53,3%) e 3 (12%) casos, respectivamente. Encontrou-se uma associaÃÃo significativa positiva entre a invasÃo linfovascular e a imunomarcaÃÃo do CXCR4 (p=0.007) e CCR7 (p=0.01) e dentre esses casos a metÃstase esteve presente em 62,5% e 37,5%, respectivamente. Quando em associaÃÃo com o Ki67, encontrou-se uma correlaÃÃo positiva significante entre o CXCR4 (p=0.0086), CXCL12 (p=0.036) e CCR7 (p=0.04). Dentre os pacientes CXCR4+, ao longo de 111 meses, apenas 38,4% estavam vivos (p=0.845), ao passo que tanto para pacientes CCR7+ (p = 0.398), quanto CXCR4+ e CCR7+ (p = 0.441), apÃs 62 meses, todos haviam ido a Ãbito. Conclui-se que essas quimiocinas estÃo associadas com a invasÃo linfovascular e proliferaÃÃo celular, talvez favorecendo o desenvolvimento de metÃstases e um pior prognÃstico.
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