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      Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions Translated title: Avaliação da expressão de Telomerase (hTert), Ki67 e p16 ink4a em lesões intraepiteliais cervicais de baixo e alto graus

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          ABSTRACT Objective : to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. Methods : we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone. We evaluated all surgical specimens for immunohistochemical expression of p16ink4a, hTert and Ki67. Results : the mean age was 38.2 years; p16ink4a was absent in most CIN I cases. In patients with CIN II or I/II (association of low and high-grade lesions), we observed p16ink4a ≤10%. In patients with CIN III, we found a higher expression frequency of p16ink4a >50%. In CIN I, the majority had Ki67≤10% and low frequency of Ki67>50%. In the CIN III category, there were fewer patients with Ki67≤10%, and Ki67 was absent in most patients of CIN II and III groups. There was no association between hTert expression and histologic grade. There were no statistically significant differences between the expression of the markers in patients with and without recurrence. Conclusion : there was a statistically significant association of p16ink4a and Ki67 with histological grade. The markers' expression, as for disease recurrence, was not statistically significant in the period evaluated.

          Translated abstract

          RESUMO Objetivo: estudar a associação entre a graduação histológica das neoplasias intraepiteliais cervicais (NIC I, NIC II e NIC III) e a expressão imuno-histoquímica para p16ink4a, hTert e Ki67, assim como, avaliar a relação destes marcadores com o risco de recorrência após tratamento cirúrgico. Métodos: estudo de coorte histórica de 94 mulheres portadoras de lesões intraepiteliais NIC I (baixo grau), NIC II e NIC III (altos graus), submetidas à conização ou à excisão eletrocirúrgica da zona de transformação. Todas as peças cirúrgicas foram avaliadas quanto à expressão imuno-histoquímica para p16ink4a, hTert e Ki67. Resultados: a média de idade das pacientes foi 38,2 anos. Nas pacientes NIC I, a p16ink4a estava ausente na maioria dos casos; nas pacientes NIC II ou I/II (associação de lesões de baixo e alto graus), observou-se frequência de p16ink4a≤10%. Nas pacientes NIC III, observou-se maior frequência de expressão de p16ink4a>50%. Na categoria NIC I, a maioria apresentava Ki67≤10% e baixa frequência de Ki67>50%. Na categoria NIC III houve menor número de pacientes com Ki67≤10%, sendo que a maior parte das pacientes tinha Ki67 ausente nos grupos NIC II e III. Não houve associação entre a expressão do marcador imuno-histoquímico hTert e a graduação histológica. Não houve diferenças estatisticamente significativas entre as expressões dos marcadores em pacientes com e sem recorrência. Conclusão: houve associação estatisticamente significativa apenas de p16ink4a e Ki67 com a graduação histológica. A expressão dos marcadores em relação à recorrência da doença não foi estatisticamente significativa no período avaliado.

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          Condylomata acuminata and human genital cancer.

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            Histology of cervical intraepithelial neoplasia and the role of biomarkers.

            Accurate histological grading of cervical intraepithelial neoplasia (CIN) lesions is important for clinical management of patients, because CIN1 and CIN2 and 3 lesions are treated differently. In general, there tends to be poor inter and intra-observer reproducibility of CIN grade evaluation among pathologists. In particular, the differential diagnosis between immature squamous metaplasia and CIN1 and 2, or between low-grade (CIN1) and high-grade (CIN2 and 3) lesions, tend to be difficult. These difficulties mean that patients tend to be over-treated for CIN lesions, which will naturally regress. Collectively, this highlights the need for alternative approaches and specific biomarkers to aid objective CIN lesion grading, and to identify true high-grade cervical disease. In this review we focus on the aetiology, pathobiology, the natural history of CIN, current issues with diagnosis and classification of CIN and the diagnostic and prognostic utility of specific biomarkers in identifying true cancerous precursor lesions. Copyright © 2011. Published by Elsevier Ltd.
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              Risk factors for cervical intraepithelial neoplasia recurrence after conization: a 10-year study.

              To evaluate the risk factors potentially involved in the development of cervical intraepithelial neoplasia (CIN) recurrence after cervical conization in a long-term follow-up period. Consecutive patients with histologically proven CIN who had undergone either cold knife conization or a loop electrosurgical excision procedure were enrolled and scheduled for serial follow-up examinations over a 10-year period. Data were stored in a digital database. Multivariate analysis was performed to identify factors for recurrence. Between January 1999 and December 2009, 282 patients fulfilled the inclusion criteria and were included in the final statistical analysis. After a median follow-up of 26.7 months (range 6-100), 64 (22.7%) women developed histologically confirmed recurrence. The 2-year recurrence-free survival was 83.7% and 66.7% for women with negative and positive margins, respectively (p=0.008). The 5-year recurrence-free survival was 75.4% and 50.3% for patients with negative and positive margins, respectively (p=0.0004). Positive surgical margin was the most important independent predictor of recurrence [HR 2.5 (95%CI 1.5-4.5), p=0.0007; Wald 11.338]. After multinomial logistic regression the indication for conization based on persistent CIN1 was the only independent predictor for negative margin [OR 0.3 (95%CI 0.1-0.7), p=0.008]. Our study demonstrated that the surgical margin status represents the most important predictor for CIN recurrence after conization. After excisional therapy, close follow-up is mandatory for the early detection of recurrent disease. The identification of risk factors for recurrence may guide clinical decision-making on expectant management versus re-intervention. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                rcbc
                Revista do Colégio Brasileiro de Cirurgiões
                Rev. Col. Bras. Cir.
                Colégio Brasileiro de Cirurgiões (Rio de Janeiro, RJ, Brazil )
                0100-6991
                1809-4546
                April 2017
                : 44
                : 2
                : 131-139
                Affiliations
                [1] Porto Alegre Rio Grande do Sul orgnamePontifícia Universidade Católica do Rio Grande do Sul orgdiv1São Lucas Hospital Brazil
                Article
                S0100-69912017000200131
                10.1590/0100-69912017002005
                1b0a6e6c-1ddf-4d83-8416-71571583d334

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

                History
                : 11 August 2016
                : 26 September 2016
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 32, Pages: 9
                Product

                SciELO Brazil


                Immunohistochemistry,Neoplasia Intraepitelial Cervical,Telomerase,Imuno-Histoquímica,Recidiva.,Cervical Intraepithelial Neoplasia,Recurrence.

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