Ki67在完全切除后的局限性肾上腺皮质癌中的主要预后作用。
Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.
作者信息
Beuschlein Felix, Weigel Jens, Saeger Wolfgang, Kroiss Matthias, Wild Vanessa, Daffara Fulvia, Libé Rosella, Ardito Arianna, Al Ghuzlan Abir, Quinkler Marcus, Oßwald Andrea, Ronchi Cristina L, de Krijger Ronald, Feelders Richard A, Waldmann Jens, Willenberg Holger S, Deutschbein Timo, Stell Anthony, Reincke Martin, Papotti Mauro, Baudin Eric, Tissier Frédérique, Haak Harm R, Loli Paola, Terzolo Massimo, Allolio Bruno, Müller Hans-Helge, Fassnacht Martin
机构信息
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
出版信息
J Clin Endocrinol Metab. 2015 Mar;100(3):841-9. doi: 10.1210/jc.2014-3182. Epub 2015 Jan 5.
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.
背景
肾上腺皮质癌（ACC）即使在完整（R0）切除术后仍频繁复发。
目的
本研究旨在确定在此临床背景下对患者具有预后价值的标志物。
设计、设置和参与者：从德国ACC登记处，确定了319例欧洲肾上腺肿瘤研究网络I - III期患者。作为独立验证队列，纳入了来自三个欧洲国家的250例患者。
结果测量和统计分析
临床、组织学和免疫组化标志物与无复发生存期（RFS）和总生存期（OS）相关。
结果
尽管德国队列中的单变量分析提示了几个具有潜在预后能力的因素，但多变量调整后，只有少数因素包括年龄、肿瘤大小、静脉瘤栓（VTT）和增殖标志物Ki67仍具有显著性。其中，Ki67对RFS（复发风险比[HR]，每增加1%为1.042；P <.0001）和OS（死亡风险比，1.051；P <.0001）提供了最佳的单一预后价值，这在验证队列中得到了证实。因此，Ki67<10%、10 - 19%和≥20%的患者临床结局有显著差异（德国队列：中位RFS，53.2对31.6对9.4个月；中位OS，180.5对113.5对42.0个月）。使用包括肿瘤大小、VTT和Ki67的联合队列建立了预后评分。尽管这些评分在亚组间的区分稍好，但与单独使用Ki67相比，没有临床意义上的优势。
结论
这项关于局限性ACC预后标志物的最大规模研究确定Ki67是预测R0切除术后患者复发的最重要单一因素。因此，应将Ki67指数评估作为所有ACC患者病理报告的标准分级引入。
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