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      Reatividade linfonodal e densidade microvascular nas metástases cervicais de carcinoma epidermóide com tumor primário oculto Translated title: Lymph node reactivity and microvessel density in neck metastases of unknown primary squamous cell carcinoma

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          Abstract

          INTRODUÇÃO: A neoangiogênese e a resposta imunológica são mecanismos importantes no desenvolvimento das metástases. OBJETIVO: Avaliar a reatividade linfonodal e a densidade microvascular nas metástases cervicais de carcinoma epidermóide com tumor primário oculto, considerando a sua relação com outras variáveis histológicas e clínicas. TIPO DE ESTUDO: Série de casos, retrospectiva. CASUÍSTICA E MÉTODO: 19 pacientes submetidos a esvaziamento cervical entre 1983 e 2000. Os linfonodos foram reavaliados quanto ao tipo de reatividade, considerando a área cortical e paracortical. Nas metástases foi avaliado o grau de diferenciação, desmoplasia, necrose, e densidade microvascular (CD34). Foi estabelecida a relação entre as diferentes variáveis histológicas e clínicas, incluindo o estadiamento e a evolução dos pacientes. RESULTADOS: A densidade microvascular apresentou mediana de 91 vasos/mm2, variando de 28 a 145. A reatividade paracortical foi mais freqüente nos pacientes com menos de 55 anos (90% x 44%, p= 0,05). A sobrevida livre de doença foi de 52% em 3 anos, sendo similar entre os pacientes com maior ou menor densidade microvascular tumoral. CONCLUSÕES: A densidade microvascular nas metástases de tumor primário oculto apresenta grande variação individual. Não foi possível estabelecer relação entre a densidade microvascular e as variáveis clínicas e histológicas estudadas.

          Translated abstract

          BACKGROUND: neoangiogenesis and the immune response are important mechanisms in metastasis development. AIM: to evaluate lymph node reactivity and microvessel density in neck metastasis of occult primary squamous cell carcinoma considering their histological and clinical variables. STUDY DESIGN: retrospesctive case-series. METHOD: 19 patients with neck metastasis of occult primary squamous cell carcinoma who underwent neck dissection between 1983 and 2000 were selected. The lymph nodes were reevaluated on the type of reactivity in both the cortical and paracortical areas, and the metastasis were assessed as to grade, desmoplasia, necrosis and microvessel density (CD34). The relationship between histological and clinical variables was evaluated. RESULTS: the median microvessel density was 91 vessels/mm2, varying from 28 to 145. Paracortical hyperplasia was more common in patients below 55 years of age (90% x 44%, p= 0.05), but there was no relationship between reactivity patterns and microvessel density with prognosis. The disease-free survival was 52% in 3 years, being similar in both groups, with higher or lower microvessel densities. CONCLUSION: microvessel density in neck metastasis of occult primary squamous cell carcinoma had a great individual variability. It wasn’t possible to establish the relationship between microvessel density and the clinical or histological variables studied.

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          Most cited references25

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          Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us.

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            Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture.

            I J Fidler (1990)
            The process of metastasis is not random. Rather, it consists of a series of linked, sequential steps that must be completed by tumor cells if a metastasis is to develop. Although some of the steps in this process contain stochastic elements, as a whole, metastasis favors the survival and growth of a few subpopulations of cells that preexist within the parent neoplasm. Moreover, metastases can have a clonal origin, and different metastases can originate from the proliferation of single cells. The outcome of metastasis depends on the interaction of metastatic cells with different organ environments. Organ-specific metastases have been demonstrated in a variety of experimental tumor systems. Moreover, we have found tumor growth that is specific to a particular site within one organ. Whether the same conclusions can be reached for human cancers remained unanswered until very recently. Studies from our laboratory and from others have shown that the implantation of human cancer cells derived from surgical specimens into correct anatomical sites of nude mice can provide a suitable model of metastasis of human tumors. Clonal analysis of a human renal carcinoma, colon carcinomas, and melanomas has revealed that these tumors are indeed heterogeneous for metastatic properties, an observation made only after orthotopic implantation. Thus, growth in the environment of specific organs can be selective and the environment per se influences this process. While it is clear that vascularity and local immunity can facilitate or retard tumor growth, we have concentrated on understanding how damage to an organ and the subsequent repair process can facilitate tumor cell proliferation. Accelerated growth of human colon cancer cells was found in hepatectomized nude mice, whereas accelerated growth of human renal cancer cells was found in nephrectomized nude mice. These data suggest that systemic physiological signals can be recognized by neoplastic cells presumably by mechanisms similar to those shared by their normal cell counterparts. In summary, the critical factors that regulate metastasis are the intrinsic properties of metastatic cells and host factors involved in homeostasis. The recent increase in our understanding of metastasis should provide important leads for developing more effective approaches to the treatment of disseminated cancer.
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              Tumor-associated macrophages: the double-edged sword in cancer progression.

              Inflammation plays a critical role in cancer progression. In this study we investigate the pro-tumorigenic activities and gene expression profiles of lung cancer cells after interaction with macrophages. We measured intratumoral microvessel counts and macrophage density in 41 lung cancer tumor specimens and correlated these with the patients' clinical outcome. The interaction between macrophages and cancer cell lines was assessed using a transwell coculture system. The invasive potential was evaluated by in vitro invasion assay. The matrix-degrading activity was assayed by gelatin zymography. The microarray was applied to a large-scale analysis of the genes involved in the interaction, as well as to monitor the gene expression profiles of lung cancer cells responding to anti-inflammatory drugs in cocultures. The macrophage density positively correlated with microvessel counts and negatively correlated with patient relapse-free survival (P < .05). After coculture with macrophages, lung cancer cell lines exhibited higher invasive potentials and matrix-degrading activities. We identified 50 genes by microarray that were upregulated more than two-fold in cancer cells after coculture. Northern blot analyses confirmed some gene expression such as interleukin-6, interleukin-8, and matrix metalloproteinase 9. The two-dimensional hierarchical clustering also demonstrated that the gene expression profiles of lung cancer cells responding to various anti-inflammatory drugs in cocultures are distinct. The interaction of lung cancer cells and macrophages can promote the invasiveness and matrix-degrading activity of cancer cells. Our results also suggest that a great diversity of gene expression occurs in this interaction, which may assist us in understanding the process of cancer metastasis.
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                Author and article information

                Journal
                rboto
                Revista Brasileira de Otorrinolaringologia
                Rev. Bras. Otorrinolaringol.
                ABORL-CCF Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial (São Paulo, SP, Brazil )
                0034-7299
                June 2006
                : 72
                : 3
                : 382-387
                Affiliations
                [01] orgnameHospital Heliópolis
                [02] orgnameCentro Universitário Positivo
                [03] orgnameEscola Paulista de Medicina
                Article
                S0034-72992006000300015 S0034-7299(06)07200315
                10.1590/S0034-72992006000300015
                64654b3e-c752-4f5d-b7bd-2696ba5c7bc4

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 28 March 2006
                : 06 January 2006
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 25, Pages: 6
                Product

                SciELO Brazil

                Categories
                Artigos Originais

                lymph nodes,linfonodos,carcinoma de células escamosas,pathologic neovascularization,neoplasias de cabeça e pescoço,neoplasias primárias desconhecidas,neovascularização patológica,squamous cell cancer,unknown primary neoplasms,head and neck neoplasms

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