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Diagnose und Graduierung zervikaler intraepithelialer Neoplasien

Diagnosis and grading of cervical intraepithelial neoplasias

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Zusammenfassung

Diagnose und Graduierung von zervikalen intraepithelialen Neoplasien (CIN) gehören zu den häufigen Fragestellungen in der histopathologischen Diagnostik. Trotzdem kann die Unterscheidung zwischen reaktiven Veränderungen und CIN1 bzw. die Graduierung einer CIN Schwierigkeiten bereiten.

In dieser Studie wurde untersucht, ob die Bestimmung der Proliferationsmarker Ki-67 und Mcm2 sowie von p16 zur Beantwortung dieser Fragestellungen beitragen. Untersucht wurden die immunhistochemischen Expressionsprofile dieser Marker an 297 Proben aus dysplasiefreiem Portioepithel, CIN1, CIN2 und CIN3 mittels Gewebemikroarrays.

Die mittels Ki-67 bzw. Mcm2 ermittelte Proliferationsrate zeigte eine Zunahme von dysplasiefreiem Epithel über CIN1, CIN2 zu CIN3 (p<0.001 bei beiden Markern). Mittels Ki-67 ließ sich am besten zwischen dysplasiefreiem Epithel und CIN1 unterscheiden. Zur Abgrenzung von CIN1 zu CIN2 bot sich eine Kombination von Ki-67 und p16 an. Bei einer Ki-67-Expression von <25% handelte es sich um eine CIN1 mit einer Sensitivität von 91,7% und einer Spezifität von 54,3%. Die zusätzliche Untersuchung der Expression von p16 konnte einen weiteren Teil der Fälle mit einer Ki-67-Expression von <25% stratifizieren. Die Anzahl p16-positiver Fälle betrug bei normalen Epithelien 0%, bei CIN1 7%, bei CIN2 46% und bei CIN3 86%. Somit war mittels p16 eine Abgrenzung der CIN2 zur CIN3 nur zum Teil möglich.

Die histopathologische Evaluation am HE-Schnitt bleibt Grundlage der Beurteilung von zervikalen intraepithelialen Neoplasien, jedoch kann die Analyse von Ki-67 und p16 zur Diagnose und Graduierung beitragen.

Abstract

Diagnosing and grading of cervical intraepithelial neoplasias (CIN) are part of the routine practice of pathologists. However, discriminating between reactive changes and CIN1 and determining the different degrees of CIN may be challenging. Aim of this study was the evaluation of the proliferation markers Ki-67 and Mcm2 as well as p16 for their potential to aid in the assessment of CIN.

297 samples of normal epithelium, CIN1, CIN2, and CIN3 were assessed for expression of the above mentioned markers using tissue microarrays.

There was an increase in the expression of Ki67 and Mcm2 from normal epithelium, CIN1, CIN2 to CIN3 (p<0.001 for both markers). Ki-67 was the most useful marker in differentiating between normal epithelium and CIN1. The number of p16-positive cases was 7% in CIN1, 46% in CIN2 and 86% in CIN3. There were no p16-positive cases in the group with normal epithelium. In order to grade CIN1 vs. CIN2 a combination of Ki-67 and p16 was helpful. Cases with a proliferation rate of <25% assessed with Ki-67 were most likely CIN1 (sensitivity 91.7%, specificity: 54.3%, positive predictive value: 73.3%, negative predictive value 82.6%). P16 was the most helpful marker in distinguishing between CIN2 and CIN 3 as p16 negative cases were more likely to belong into the CIN2 category.

In summary, the histopathological assessment of cervical biopsies is based on H&E-stained slides. However, Ki-67 and p16 can be helpful in diagnosing and grading cervical intraepithelial neoplasia.

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Danksagung

Ganz besonderer Dank gilt Fr. PD Dr. I. Zlobec, Institut für Pathologie der Universität Bern für die statistische Auswertung und die hilfreichen Diskussionen. Für technische Unterstützung bedanken sich die Autoren bei Fr. T. Nguyen.

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  1. Institut für Pathologie, Universitätsspital Basel, Schönbeinstr. 40, 4031, Basel, Schweiz

    C. Rosamilia, G. Feichter, A. Tzankov &  E.C. Obermann

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  1. C. Rosamilia
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  2. G. Feichter
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  3. A. Tzankov
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  4. E.C. Obermann
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Correspondence to E.C. Obermann.

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Die vorgestellten Ergebnisse sind Anteile der Dissertationsschrift von C.R.

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Rosamilia, C., Feichter, G., Tzankov, A. et al. Diagnose und Graduierung zervikaler intraepithelialer Neoplasien. Pathologe 33, 118–123 (2012). https://doi.org/10.1007/s00292-011-1549-5

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