title: Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medizinische Klinik and Poliklinik IV (F.B., A.O., M.R., M.F.), Ludwig-Maximilians-Universität München, D-80336 Germany; Department of Medicine I, Endocrine and Diabetes Unit (J.W., C.L.R., T.D., B.A., M.F.), University Hospital, University of Würzburg, D-97080 Germany; Department of Pathology (W.S.), University of Hamburg, D-20246 Germany; Comprehensive Cancer Center Mainfranken (M.K., M.F.), University of Würzburg, D-97080 Germany; Institute of Pathology (V.W.), University of Würzburg, D-97080 Germany; Medicina Interna 1 (F.D., A.A., M.T.), Azienda Ospedalier Universitaria San Luigi and University of Turin, I-10043, Italy; Département d'Endocrinologie (R.L.), Groupe hospitalier Cochin, F-75104, France; Institut Gustave Roussy (A.A.G., E.B.), F-94805, France; Clinical Endocrinology (M.Q.), Campus Mitte, University Hospital Charité, D-10117, Germany; Department of Pathology (R.D.K.), Erasmus Medical Center, N-3000, Netherlands; Department of Internal Medicine (R.A.B.), Erasmus Medical Center, N-3000, Netherlands; Department of Visceral, Thoracic and Vascular Surgery (J.W.), University Hospital Giessen and Marburg, Campus Marburg, D-35033 Marburg; Department of Endocrinology and Diabetology (H.S.W.), University of D-40225 Düsseldorf, Germany; Melbourne eResearch Group (D.A.S.), University of Melbourne, VIC 3010 Melbourne; Anatomia Patologica (M.P.), Azienda Ospedalier Universitaria San Luigi and University of Turin, I-10043, Italy; Department of Pathology (F.T.), Pitié-Salpêtrière, AP-HP, Pierre and Marie Curie University, Sorbonne Universités; Inserm U1016, Institut Cochin, UMR8104, Université Paris Descartes, Sorbonne Paris Cité, F-75014 Paris; Máxima Medisch Centrum (H.R.H.), N-5600, Netherlands; Ospedale Niguarda Cà Granda (P.L.), I-20122, Italy; Institute for Medical Informatics, Biometry and Epidemiology (H.-H.M.), Ludwig-Maximilians-Universität München, D-81377 München; Central laboratory (M.F.), University Hospital Würzburg, University of 
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mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery*; D000315:Adrenalectomy; D018268:Adrenocortical Carcinoma / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen