Pennanen Mirkka, Hagström Jaana, Heiskanen Ilkka, Sane Timo, Mustonen Harri, Arola Johanna, Haglund Caj
Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland.
Department of Surgery, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland.
J Clin Pathol. 2018 Feb;71(2):129-134. doi: 10.1136/jclinpath-2017-204503. Epub 2017 Aug 11.
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.
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.
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.
Strong cytoplasmic c-myc expression and weak nuclear expression in adrenocortical tumours associated with malignancy and shorter survival.
高分辨率成像技术的广泛应用以及肾上腺病变患病率的增加，使得肾上腺皮质肿瘤的诊断成为一个日益重要的临床问题。对于非转移性肿瘤，诊断基于组织学。通过生物标志物可能会出现用于临床病理诊断的新的或增强的信息，揭示肿瘤的恶性潜能。原癌基因c-myc与肾上腺皮质肿瘤的联系鲜为人知，尽管Wnt/β-连环蛋白信号通路（导致c-myc表达诱导的信号通路之一）已与肾上腺皮质肿瘤的发生相关。我们研究了肾上腺皮质肿瘤中c-myc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。
我们研究了195例连续的成年患者，他们患有197个原发性肾上腺皮质肿瘤。组织病理学诊断通过Weiss评分和新的赫尔辛基评分确定。通过免疫组织化学测定c-myc、细胞周期蛋白D1、细胞周期蛋白E和p27的表达。
良性腺瘤显示出与正常肾上腺皮质细胞相当的显著核c-myc表达，而癌显示出细胞质表达增加。强细胞质和弱核c-myc表达与恶性肿瘤和不良预后相关。c-myc染色与细胞周期蛋白E不相关。细胞周期蛋白D1与细胞质c-myc表达相关，与核c-myc的相关性较小。P27与细胞质c-myc相关，但与核c-myc不相关。P27与细胞周期蛋白E相关。
肾上腺皮质肿瘤中强细胞质c-myc表达和弱核表达与恶性肿瘤和较短生存期相关。
