摘要：局限于肾上腺的低级别肾上腺皮质癌(adrenal cortical carcinoma, ACC)诊断可能有一定挑战性。尽管已有一些ACC诊断与预后相关的分子检测，但仍未得到广泛应用。我们在包括50例腺瘤及43例腺癌的组织芯片中，从严格定义的血管侵犯、Weiss评分、核分裂基础上的肿瘤分级，研究了网状结构异常及部分生物标志物免疫组化表达的诊断及预后价值，这些生物标志物包括IGF-2、细胞增殖及有丝分裂纺锤体调节相关蛋白（Ki-67、p53、BUB1B、HURP、NEK2）、DNA损伤修复相关蛋白（PBK、γ-H2AX）、端粒调节相关蛋白（DAX、ATRX）、wnt信号通路相关蛋白（β－连蛋白）和PI3K信号通路相关蛋白(PTEN、磷酸化-mTOR）。结果提示，IGF-2及细胞增殖和有丝分裂纺锤体调节相关蛋白（Ki-67、p53、BUB1B、HURP、NEK2）、ＤＮＡ损伤修复相关蛋白（PBK、γ-H2AX）、端粒调节相关蛋白（DAX、ATRX）和β－连蛋白均呈现特征性表达模式，可区分癌和腺瘤。但并非所有生物标志物在所有癌中均有意义。IGF-2是最有价值的恶性标志物，其与肿瘤分级、细胞形态学特征无关，在80%以上的癌中呈核旁高尔基体特异性高表达，而腺瘤则无此表达。癌和腺瘤之间有显著差异的是网状骨架缺失，而不是其性质改变。将肿瘤细胞侵透血管壁间或混有血栓的癌栓定义为血管侵犯，证明是最佳的预后指标，可预测本组肿瘤及低级别ACC的不良结局。肿瘤低核分裂计数和Weiss评分、DAXX表达缺失和磷酸化-mTOR高表达均与患者无病生存相关；但Weiss评分和生物标志物不能预测低级别病变的不良预后。我们的结果强调，细致的形态学评估结合ACC诊断与预后相关生物标志物检测具有重要价值。
关键词：血管侵犯，IGF-2，肾上腺皮质癌，网状蛋白，生物标志物，Ki-67，磷酸化-mTOR，DAXX，肿瘤分级
Am J Surg Pathol 2018；42:201-213
美国外科病理学杂志中文版2018年第二期全文No.1
王强/沈士亮 翻译 阎晓初 审校
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