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      Presença da Proteína p53 como Prognóstico de Recidiva/Progressão de Neoplasia Intra-epitelial Vulvar III Translated title: p53 Protein Overexpression as a Prognostic Marker for Vulvar Intraepithelial Neoplasia III Recurrence/Progression

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          Abstract

          Objetivo: avaliar o valor da presença da proteína p53 nos casos de recidiva/progressão da neoplasia intra-epitelial vulvar (VIN) III. Métodos: foram selecionadas 20 pacientes com VIN III indiferenciada, seguidas semestralmente por período de até quatro anos, divididas em dois grupos: quatorze sem e seis com recidiva/progressão da lesão. Os casos de recidiva/progressão foram distribuídos da seguinte forma: em três pacientes a recidiva ocorreu uma única vez, em duas, houve dupla recorrência e apenas uma evoluiu para carcinoma escamoso. Em ambos os grupos foram avaliados o sítio vulvar acometido e a presença da proteína p53 com análise do padrão de marcação imunohistoquímica. Estudo semelhante foi realizado nos casos de recidiva/progressão além da análise do intervalo de tempo para o surgimento de recidiva/progressão. Resultados: observou-se recidiva da VIN III em 25% dos casos e, em 5%, progressão para carcinoma. O tempo médio de recidiva foi de 24,5 meses. A localização multifocal da lesão primária foi a mais freqüente (50%) em ambos os grupos. Na maioria dos casos (87,5%), a recidiva/progressão ocorreu na mesma localização da lesão vulvar primária. A presença da proteína p53 mostrou-se positiva em 50% das lesões primárias de VIN III e em 75% dos casos de recidiva/progressão. Conclusões: a presença da proteína p53 parece desempenhar papel importante na gênese e na predição do curso clínico das VIN III. As recidivas/progressão das VIN III tendem a ocorrer na mesma área da doença inicial, sugerindo a presença de campo molecular alterado.

          Translated abstract

          Purpose: to evaluate p53 overexpression value in vulvar intraepithelial neoplasia (VIN) III recurrence/progression. Methods: twenty patients with undifferentiated VIN III were selected and followed up every six months for four years and divided into two groups: fourteen without and six with recurrence/progression lesion. The recurrence/progression cases were distributed as follows: in three patients recurrence occurred only once; in two, twice, and only one progressed to squamous cancer. In both groups the site of vulvar lesion and p53 overexpression and immunostaining pattern were analyzed. A similar study was performed in recurrence/progression cases, besides the analysis of the time interval to occur the arise of recurrence/progression. Results: recurrence was observed in 25% of the cases and, in 5%, progression to carcinoma. The mean time interval for recurrence was 24.5 months. Multifocal location of the initial lesion was the predominant form (50%) in both groups. In the majority of the cases (87.5%) recurrence/progression occurred at the same site of the initial vulvar lesion. p53 overexpression was observed in 50% of the VIN III primary lesions and in 75% of the recurrence/progression cases. Conclusions: p53 overexpression seems to play an important role in VIN III pathogenesis and may predict the clinical course of the lesions. VIN III recurrence/progression has a tendency to occur in the same area of the initial lesion, suggesting the presence of molecular disturbance.

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          The cellular response to p53: the decision between life and death.

          The p53 tumor suppressor protein plays a crucial role in regulating cell growth following exposure to various stress stimuli. p53 induces either growth arrest, which prevents the replication of damaged DNA, or programmed cell death (apoptosis), which is important for eliminating defective cells. Whether the cell enters growth arrest or undergoes apoptosis, depends on the final integration of incoming signals with antagonistic effects on cell growth. Many factors affect the cellular response to activated p53. These include the cell type, the oncogenic status of the cell with emphasis on the Rb/E2F balance, the extracellular growth and survival stimuli, the intensity of the stress signals, the level of p53 expression and the interaction of p53 with specific proteins. p53 is regulated both at the levels of protein stability and biochemical activities. This complex regulation is mediated by a range of viral and cellular proteins. This review discusses this intriguing complexity which affects the cell response to p53 activation.
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            Predicting response to cancer chemotherapy: the role of p53.

            Loss of wild-type p53 activity is thought to be a major predictor of failure to respond to radiotherapy and chemotherapy in various human cancers. This assumption is largely based on some cell-death studies in p53-knockout mice and on correlations of p53 status assessed by immunochemistry or single-strand conformational polymorphism (SSCP) analysis, and responses to therapy in human cancers in vivo. In principle, p53 may enhance chemosensitivity by promoting apoptosis via transcription-independent mechanisms as well as transcriptional activation of proapoptotic genes such as bax and transcriptional repression of antiapoptotic genes such as bcl-2. Drug-induced suicide mediated by the CD95/CD95 ligand system may also involve a p53-controlled pathway. Yet, p53 may decrease chemosensitivity by promoting p21-mediated and p21-independent growth arrest, DNA repair, and differentiation, and by enhancing the transcription of antiapoptotic genes such as bcl-x. Cell-culture work indicates that the effects of altering the p53 status on chemosensitivity depend very much on the cellular context. Disruption of p53 function in otherwise normal, nonneoplastic cells may enhance rather than decrease chemosensitivity. However, targeted p53 gene disruption in some cell types obtained from p53-knockout mice results in enhanced rather than decreased sensitivity, e.g., to irradiation. Transformed cells that have retained wild-type p53 function tend to acquire chemoresistance when p53 function is disabled, with few exceptions. Thus, preexisting molecular alterations or consecutive accumulation of molecular alterations after loss of p53 rather than the loss of wild-type p53 activity per se may confer chemoresistence to tumor cells. Moreover, p53 accumulation resulting from the increased half-life of mutant p53 proteins can act as a gain-of-function mutation, presumably as a consequence of multiple protein-protein interactions. Finally, significant tumor cell-type- and drug-specific patterns of modulation of chemosensitivity by p53 are beginning to emerge. Transfer of wild-type p53 genes into tumor cells commonly induces growth arrest but may render these cells relatively more resistant to most chemotherapeutic drugs. Therefore, careful experimental in vitro and in vivo studies are required before chemotherapy-supported p53 gene therapy for human cancer is introduced into clinical practice.
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              p53 as a prognostic factor in stage I breast cancer

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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rbgo
                Revista Brasileira de Ginecologia e Obstetrícia
                Rev. Bras. Ginecol. Obstet.
                Federação Brasileira das Sociedades de Ginecologia e Obstetrícia (Rio de Janeiro )
                1806-9339
                January 2002
                : 24
                : 1
                : 51-57
                Affiliations
                [1 ] Universidade Federal do Rio de Janeiro Brazil
                [2 ] Universidade Federal do Rio de Janeiro Brazil
                [3 ] Universidade Federal do Rio de Janeiro Brazil
                [4 ] Faculdade de Medicina de Campos
                Article
                S0100-72032002000100008
                10.1590/S0100-72032002000100008
                9bb6512d-37a4-4618-985a-c4ada7e305a1

                http://creativecommons.org/licenses/by/4.0/

                History
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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0100-7203&lng=en
                Categories
                OBSTETRICS & GYNECOLOGY

                Obstetrics & Gynecology
                Vulvar intraepithelial neoplasia,Vulva: preneoplastic lesions,Oncogenes,Neoplasia intra-epitelial vulvar,Vulva, lesões pré-neoplásicas

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