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Rev Bras Ginecol Obstet 2016; 38(02): 082-087
DOI: 10.1055/s-0036-1571470
Original Article
Thieme Publicações Ltda Rio de Janeiro, Brazil

Expression of the Immunohistochemical Markers p16 and Ki-67 and Their Usefulness in the Diagnosis of Cervical Intraepithelial Neoplasms

Reprodutibilidade do diagnóstico das neoplasias intraepiteliais cervicais e a influência dos marcadores imuno-histoquímicos p16 e Ki-67 como ferramentas auxiliares
Fernanda Lopes Pontes de Melo
1   Master's Program in Health Sciences, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil
,
Carmen Lúcia Penteado Lancellotti
2   Pathological Anatomy Course, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil
,
Maria Antonieta Longo Galvão da Silva
3   Pathological Anatomy Course, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil
› Author Affiliations
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Publication History

10 July 2015

19 November 2015

Publication Date:
03 February 2016 (online)

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Abstract

Objective The aim of this study was to determine the expression of the immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasms and their influence on the level of agreement among different observers and for the same observer.

Methods The study included 184 patients with cervical intraepithelial neoplasms previously confirmed through biopsies performed between 2005 and 2006. Three pathologists reviewed the biopsies by using hematoxylin-eosin staining to reach a consensus on the diagnosis. Subsequently, an immunohistochemical study analyzed the expression of p16 and Ki-67 in such cases.

Results The comparison among the reviewing pathologists revealed only moderate agreement (kappa = 0.44). The agreement improved when the differentiation of high-grade lesions (cervical intraepithelial neoplasm – CIN – 3) was analyzed (kappa = 0.59). p16 staining exhibited a high negative predictive value and sensitivity; however, the specificity was low. Overall, both qualitative and quantitative analyses of p16 and a quantitative analysis Ki-67 exhibited low accuracy. The agreement among diagnoses before immunohistochemistry was 0.47. The use of immunohistochemistry increased the agreement to 0.68.

Conclusion Our study showed that the agreement among observers using traditional diagnostic criteria of cervical intraepithelial lesions can improve with the use of immunohistochemistry.

Resumo

Objetivo Observar a expressão dos marcadores imuno-histoquímicos p16 e Ki-67 em neoplasias intraepiteliais cervicais e sua influência na concordância entre observadores diferentes e, entre o mesmo observador.

Métodos Foram incluídas no estudo 184 pacientes com neoplasias cervicais intraepiteliais confirmadas por biópsia realizadas durante os anos de 2005 e 2006. As biópsias foram revistas, primeiramente, por três patologistas utilizando-se apenas a coloração de Hematoxilina-Eosina. Foi realizado um consenso acerca do diagnóstico. Posteriormente, foi realizado o estudo imuno-histoquímico e analisada a expressão de p16 e Ki-67 nesses casos.

Resultados A comparação entre os patologistas revisores mostrou uma concordância apenas regular (k = 0,44. A concordância foi melhor quando analisada apenas a capacidade de diferenciar lesões de alto grau (NIC 3) (k = 0,59). 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 os diagnósticos antes da imuno-histoquímica obteve k = 0,47, e após o auxílio da imuno-histoquímica houve um aumento do Kappa para 0,68. 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.

Conclusão Nosso estudo mostrou que a concordância no diagnóstico tradicional de lesões intraepiteliais cervicais é regular e que pode ser melhorada como o auxílio da imuno-histoquímica.

Keywords

cervical intraepithelial neoplasia - HPV - p16 - Ki-67 - kappa

Palavras -chave

neoplasia intraepitelial cervical - HPV - p16 - Ki-67 - kappa
 

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