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Detektion der lymphovaskulären Invasion mit D2-40-Immunhistochemie beim Urothelkarzinom der Harnblase

Detection of lymphovascular invasion in urothelial carcinoma of the bladder through D2-40 immunostaining

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Zusammenfassung

Hintergrund

Die lymphovaskuläre Invasion (LVI) gilt als wichtiger Prognosefaktor für die Rezidivbildung bei Patienten mit lokal begrenztem Urothelkarzinom der Harnblase (UCB) nach radikaler Zystektomie (RZE). Wir untersuchten die Bedeutung des immunhistochemischen (IHC-)Markers D2-40 für die Detektion einer LVI im Vergleich zur konventionellen Hämatoxylin-Eosin- (HE-)Färbung.

Material und Methoden

Es erfolgten HE- und IHC-Färbungen mittels D2-40-Antikörper repräsentativer Schnitte von 80 Patienten nach RZE. Alle Tumorschnitte wurden reevaluiert und verblindet auf das Vorhandensein einer LVI untersucht.

Ergebnisse

In der in HE-Färbung zeigten 53 Patienten (66,3 %) und in der IHC 44 Patienten (55 %) eine LVI. 13 Patienten (16,3 %) wiesen eine LVI nur in der HE-Färbung (HE-Färbung falsch-positiv; IHC als Referenz betrachtet) auf. Mittels D2-40 konnte bei 4 zusätzlichen Patienten (5 %) eine LVI diagnostiziert werden (falsch-negativ). 52 Patienten (65 %) wurden als pN0 klassifiziert, davon zeigten 21 (40,4 %) eine LVI in der HE- und 16 (30,8 %) eine LVI in der IHC-Färbung. Bei 9 Patienten im Stadium pN0 (17,3 %) wurde eine LVI durch IHC nicht bestätigt (falsch-positiv). Die IHC detektierte bei 4 zusätzlichen Patienten (7,7 %) eine LVI (falsch-negativ). Von diesen erlitten 3 Patienten ein Rezidiv des UCB. Bei Patienten mit Krankheitsrezidiv (n = 35) und pN0 zum Zeitpunkt der RZE zeigte die HE-Färbung bezüglich einer LVI falsch-positive Resultate bei 2 (5,7 %) und falsch-negative Ergebnisse bei 3 Patienten (8,6 %).

Schlussfolgerung

Die IHC mit D2-40 verändert die Detektionsraten der LVI im Vergleich zur konventionellen HE-Färbung. Ein routinemäßiger Einsatz der D2-40-IHC kann die Risikostratifizierung von Patienten ohne Lymphknotenmetastasen verbessern und für das Design innovativer klinischer Studien dienen.

Abstract

Background

Lymphovascular invasion (LVI) represents a surrogate marker for micrometastatic urothelial carcinoma of the bladder (UCB).

Objectives

We evaluated whether D2-40 immunhistochemistry (IHC) alters detection of LVI when compared to conventional HE (hematoxylin–eosin) staining of UCB specimens in a blinded fashion.

Material and methods

HE- and D2-40-IHC-stained representative sections of 80 patients after radical cystectomy (RC) were re-reviewed. LVI detection rates were recorded and compared after blinded evaluation.

Results

LVI was present in 53 patients (66.3%) in HE-stained sections and in 44 patients (55%) in D2-40 stainings. In 13 patients, LVI (16.3%) was found in HE stained sections but not confirmed when IHC was applied (false positive when using IHC as a reference standard). D2-40 IHC identified LVI in 4 additional patients (5%) who were classified as LVI negative in conventional HE staining (false negative). 52 patients (65%) were lymph node negative (pN0), 21 of whom (40.4%) were LVI positive in conventional HE sections and 16 of whom (30.8%) were LVI positive in IHC. In 9 pN0 patients (17.3%), LVI was diagnosed in HE sections but not confirmed by IHC (false positive). D2-40 IHC identified LVI in 4 additional patients (7.7%) who were node negative and classified as LVI negative in conventional HE staining (false negative). In patients who experienced recurrence (n=35) and who were classified as pN0 at the time of RC, HE staining resulted both in false-positive (n=2; 5.7%) and false-negative (n=3; 8.6%) findings.

Conclusion

Different detection rates of LVI were observed when using IHC with D2-40 in UCB patients compared to conventional HE staining. The routine use of D2-40 IHC should be considered in clinical trial design to improve risk stratification of pN0 patients after RC.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. T. Martini, P. Ströbel, A. Steidler, N. Petrakopoulou, P. Erben und C. Bolenz geben an, dass kein Interessenkonflikt besteht. Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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Authors and Affiliations

  1. Klinik für Urologie, Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer 1–3, 68167, Mannheim, Deutschland

    T. Martini, A. Steidler, P. Erben &  C. Bolenz

  2. Institut für Pathologie, Universitätsmedizin Göttingen, Göttingen, Deutschland

    P. Ströbel

  3. Institut für Pathologie, Universitätsmedizin Mannheim, Mannheim, Deutschland

    N. Petrakopoulou

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  1. T. Martini
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  2. P. Ströbel
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  3. A. Steidler
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  4. N. Petrakopoulou
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  5. P. Erben
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  6. C. Bolenz
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Correspondence to C. Bolenz.

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Martini, T., Ströbel, P., Steidler, A. et al. Detektion der lymphovaskulären Invasion mit D2-40-Immunhistochemie beim Urothelkarzinom der Harnblase. Urologe 54, 70–75 (2015). https://doi.org/10.1007/s00120-014-3646-6

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  • DOI: https://doi.org/10.1007/s00120-014-3646-6

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