C-myc expression in adrenocortical tumours

C-myc expression in adrenocortical tumours
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DOI:
10.1136/jclinpath-2017-204503
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发表时间:
2018-02-01
影响因子:
3.4
通讯作者:
Haglund, Caj
Haglund, Caj
中科院分区:
医学3区
文献类型:
--
作者:
Pennanen, Mirkka;Hagstrom, Jaana;Haglund, Caj

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高分辨率成像技术的广泛应用,肾上腺病变的发病率增加,使肾上腺皮质肿瘤的诊断成为一个日益重要的临床问题。在非转移性肿瘤中,诊断基于组织学。新的或增强的临床病理诊断信息,揭示肿瘤的恶性潜力,可以通过生物标志物的方式出现。原癌基因c-myc与肾上腺皮质瘤形成的联系知之甚少,尽管Wnt/β-连环蛋白通路(导致c-myc表达诱导的信号通路之一)与肾上腺皮质瘤形成有关。我们研究了c-myc在肾上腺皮质肿瘤中的表达,并研究了与c-myc信号通路相关的分子,包括细胞周期相关蛋白p27、细胞周期蛋白E和细胞周期蛋白D1。组织学诊断采用韦斯评分和新的赫尔辛基评分。结果良性腺瘤细胞核c-myc表达与正常肾上腺皮质细胞相当,而腺癌细胞质c-myc表达增加。强胞浆和弱核c-myc表达与恶性肿瘤和不良预后相关。C-myc染色与cyclin E无相关性。细胞周期蛋白D1与细胞质c-myc表达相关,在较小程度上与细胞核c-myc表达相关。P27与胞浆c-myc相关,而与胞核c-myc无关。P27与细胞周期蛋白E相关。结论肾上腺皮质肿瘤细胞质c-myc强表达和细胞核c-myc弱表达与肿瘤恶性程度和生存期缩短有关。
Aims Widespread use of high-resolution imaging techniques and thus increased prevalence of adrenal lesions has made diagnostics of adrenocortical tumours an increasingly important clinical issue. In non-metastatic tumours, diagnosis is based on histology. New or enhanced information for clinicopathological diagnosis, revealing the malignant potential of the tumour, could emerge by means of biomarkers. The connection of proto-oncogene c-myc to adrenocortical neoplasias is poorly known, although the Wnt/beta-catenin pathway, one of the signalling pathways leading to induction of c-myc expression, has been connected to development of adrenocortical neoplasias. We studied c-myc expression in adrenocortical tumours and investigated molecules associated with the signalling pathway of c-myc, including cell cycle-related proteins p27, cyclin E and cyclin D1.Methods We studied 195 consecutive adult patients with 197 primary adrenocortical tumours. Histopathological diagnosis was determined by Weiss score and the novel Helsinki score. C-myc, cyclin D1, cyclin E and p27 expressions were determined by immunohistochemistry.Results Benign adenomas showed prominent nuclear c-myc expression comparable to that of normal adrenocortical cells, whereas carcinomas showed increased cytoplasmic expression. Strong cytoplasmic and weak nuclear c-myc expressions associated with malignancy and adverse outcome. C-myc staining did not correlate with cyclin E. Cyclin D1 correlated with cytoplasmic c-myc expression and to a lesser extent with nuclear c-myc. P27 correlated with cytoplasmic c-myc, but not with nuclear c-myc. P27 correlated with cyclin E.Conclusions Strong cytoplasmic c-myc expression and weak nuclear expression in adrenocortical tumours associated with malignancy and shorter survival.