Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection

Felix Beuschlein, Jens Weigel, Wolfgang Saeger, Matthias Kroiss, Vanessa Wild, Fulvia Daffara, Rosella Libé, Arianna Ardito, Abir Al Ghuzlan, Marcus Quinkler, Andrea Oßwald, Cristina L. Ronchi, Ronald De Krijger, Richard A. Feelders, Jens Waldmann, Holger S. Willenberg, Timo Deutschbein, Anthony Stell, Martin Reincke, Mauro PapottiEric Baudin, Frédérique Tissier, Harm R. Haak, Paola Loli, Massimo Terzolo, Bruno Allolio, Hans Helge Müller, Martin Fassnacht

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

246 Citaten (Scopus)


Background: Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently. Objective: The aim of this study was to identify markers with prognostic value for patients in this clinical setting. Design, Setting, and Participants: From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included. Outcome Measurements and Statistical Analysis: Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS). Results: Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone. Conclusion: This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.

Originele taal-2Engels
Pagina's (van-tot)841-849
Aantal pagina's9
TijdschriftJournal of Clinical Endocrinology and Metabolism
Nummer van het tijdschrift3
StatusGepubliceerd - 1 mrt. 2015
Extern gepubliceerdJa


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