Nosso estudo mostra que há expressão de p16 e Ki-67 em neoplasias intraepiteliais do colo uterino e que essa expressão é mais comum em lesões de alto grau.
Analisados como marcadores diagnósticos independentes, os marcadores imunohistoquímicos não demonstram acurácia adequada.
O valor preditivo negativo do p16, contudo, se mostrou útil como ferramenta para ajudar a selecionar casos que necessitam de revisão mais atenta.
Nosso estudo confirma que a reprodutibilidade do diagnóstico convencional de neoplasias intraepiteliais cervicais é no máximo regular, mas que pode ser melhorada com a utilização da imunohistoquímica.
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8 RESUMO
De Melo FLP. Estudo da expressão dos marcadores imunohistoquímicos p16 e
Ki-i67 e de sua utilidade diagnóstica em neoplasias intraepiteliais escamosas do colo uterino. São Paulo; 2015. [Dissertação de Mestrado – Faculdade de
Ciências Médicas da Santa Casa de São Paulo]
Apesar da existência de critérios diagnósticos para graduar as neoplasias intraepiteliais cervicais, a aplicação destes critérios, por cada patologista, está sujeito a certo grau de subjetividade, levando à variação de diagnósticos. Já está demonstrado na literatura que o grau de reprodutibilidade entre observadores diferentes é no máximo moderado, quando se utiliza apenas a coloração de Hematoxilina-Eosina (HE), apesar de ser este ainda o padrão ouro. Alguns estudos têm apontado que o uso de marcadores, principalmente p16 e Ki-67, pode melhorar a reprodutibilidade. Desenhamos então um estudo para observar a expressão dos marcadores imunohistoquímicos p16 e Ki-67 em neoplasias intraepiteliais cervicais e sua influência na concordância entre observadores diferentes e, entre o mesmo observador. A casuística contou com 184 pacientes com neoplasias cervicais intraepiteliais enviadas ao Serviço de Anatomia Patológica da Santa Casa de São Paulo entre os anos 2005 e 2006. Todos os casos foram revistos por 3 patologistas que chegaram a um diagnóstico de consenso, que foi utilizado como padrão ouro. A expressão de p16 e Ki-67 pôde ser analisada em 153 casos. A comparação entre os patologistas revisores mostrou uma concordância moderada (k = 0,44), e regular entre o diagnóstico original e o consenso (k = 0,33). A concordância foi melhor quando analisada apenas a capacidade de diferenciar lesões de alto grau (NIC 3) (k=0,598). A marcação de p16 mostrou alto valor preditivo negativo e sensibilidade, porém baixa especificidade. Em geral, tanto p16 qualitativo, quanto p16 quantitativo e Ki-67 quantitativo mostraram baixa acurácia geral. A concordância entre o mesmo observador antes e depois da imunohistoquímica foi baixa (k = 0,398). A concordância aumentou entre o patologista e o consenso (k = 0,475 antes da
imunohistoquímica) com o auxílio da imunohistoquímica (k = 0,689 depois da imunohistoquímica). Nosso estudo mostrou que a concordância no diagnóstico tradicional de lesões intraepiteliais cervicais inter-observador é regular e que pode ser melhorada como o auxílio da imunohistoquímica.
9 ABSTRACT
De Melo FLP. Study of the expression of the immunohistochemical markers p16
and Ki-67 and their usefulness in the diagnostic of cervical intraepithelial neoplasms. São Paulo; 2015. [Dissertação de Mestrado – Faculdade de Ciências
Médicas da Santa Casa de São Paulo]
Despite the existence of diagnostic criteria for cervical intraepithelial neoplasia, the application of these criteria by each pathologist is subject to some degree of subjectivity, leading to variations in diagnoses. It is reported in the literature that the reproducibility between different observers is in the most moderate, when using only the histochemical method Hematoxilin-Eosin (HE), although this method is continued to be used as the gold standard. Some studies have shown that by using immunohistochemical markers, especially p16 and Ki-67, one can improve the reliability of the test. We designed a study to observe the expression of immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasia and its influence on the agreement between different observers and within the same observer in different times. The study sample included 184 patients with intraepithelial cervical neoplasia recorded in the Pathology Department of Santa Casa de São Paulo between years 2005 and 2006. Three pathologists reviewed all
cases and established a consensus diagnosis to be used as the gold standard. The
expression of p16 and Ki-67 could be analyzed in 153 cases. The reliability between the reviewers showed moderate agreement (k = 0.44), and between the initial diagnosis and the consensus only fair (k = 0.33). The agreement was better when where analyzed only the power to differentiate high-grade CIN 3 lesions (k = 0.598). When analyzed as a independent diagnostic test, p16 showed high negative predictive value and sensitivity, however low specificity. In general, however, both qualitative p16 and quantitative p16 and Ki-67 showed low overall accuracy. The agreement between the same observer before and after the immunohistochemistry was fair (k = 0.398), but the agreement between a single pathologist and the
consensus was increased (k = 0.475 without immunohistochemistry) using immunohistochemistry markers (k = 0,689 with immunohistochemistry).