Liu Xiaohai, Feng Ming, Zhang Ye, Dai Congxin, Sun Bowen, Bao Xinjie, Deng Kan, Yao Yong, Wang Renzhi
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
Department of Thoracic surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
World Neurosurg. 2018 May;113:e213-e221. doi: 10.1016/j.wneu.2018.01.214. Epub 2018 Feb 9.
Matrix metalloproteinase-9 (MMP-9), pituitary tumor transforming gene (PTTG), and high mobility group A 2 (HMGA2) play important roles in the tumorigenesis of adrenocorticotrophic hormone (ACTH)-secreting pituitary tumors, but their associations with tumor recurrence after transsphenoidal adenomectomy remain unclear. The aim of the study was to investigate the immunohistochemical expression profiles of MMP-9, PTTG, HMGA2, and Ki-67 in recurrent and nonrecurrent ACTH-secreting pituitary tumors and to identify their associations with tumor behavior and recurrence status.
A retrospective study was performed including 55 patients with sporadic Cushing's disease with long-term remission after transsphenoidal adenomectomy. Fifty-five ACTH-secreting pituitary tumor specimens and 2 normal pituitary glands were collected. After an intensive follow-up (33-59 months, mean 41.8 months), patients were divided into 2 groups based on their recurrence status: the nonrecurrent group (n = 28) and the recurrent group (n = 27). The expression of MMP-9, PTTG, HMGA2, and Ki-67 in each sample was examined and quantified by immunohistochemistry. The association between MMP-9, PTTG, HMGA2, and Ki-67 expression and clinicopathologic characteristics and tumor recurrence were evaluated.
There was a significantly increased expression of MMP-9 in the recurrent group compared with the nonrecurrent group (P = 0.022), and this was strongly associated with the recurrence-free interval (P = 0.007, correlation coefficient. = -0.354). PTTG, HMGA2, and Ki-67 expression were not significantly different between the recurrent group and the nonrecurrent group. No expression of MMP-9, PTTG, HMGA2, or Ki-67 was detected in the 2normal pituitary glands.
ACTH-secreting pituitary tumors with greater levels of MMP-9 were associated with a greater recurrence rate and a shorter recurrence-free interval. MMP-9 could be a valuable tool for predicting recurrence of ACTH-secreting pituitary tumors.
基质金属蛋白酶-9（MMP-9）、垂体肿瘤转化基因（PTTG）和高迁移率族蛋白A2（HMGA2）在促肾上腺皮质激素（ACTH）分泌型垂体肿瘤的发生发展中起重要作用，但它们与经蝶窦腺瘤切除术后肿瘤复发的关系尚不清楚。本研究旨在探讨MMP-9、PTTG、HMGA2和Ki-67在复发性和非复发性ACTH分泌型垂体肿瘤中的免疫组化表达谱，并确定它们与肿瘤行为和复发状态的关系。
进行一项回顾性研究，纳入55例经蝶窦腺瘤切除术后长期缓解的散发性库欣病患者。收集55份ACTH分泌型垂体肿瘤标本和2份正常垂体组织。经过密集随访（33 - 59个月，平均41.8个月），根据患者的复发状态将其分为两组：非复发组（n = 28）和复发组（n = 27）。通过免疫组化检测并定量每个样本中MMP-9、PTTG、HMGA2和Ki-67的表达。评估MMP-9、PTTG、HMGA2和Ki-67表达与临床病理特征及肿瘤复发之间的关联。
与非复发组相比，复发组中MMP-9的表达显著增加（P = 0.022），且这与无复发生存期密切相关（P = 0.007，相关系数 = -0.354）。复发组和非复发组之间PTTG、HMGA2和Ki-67的表达无显著差异。在2份正常垂体组织中未检测到MMP-9、PTTG、HMGA2或Ki-67的表达。
MMP-9水平较高的ACTH分泌型垂体肿瘤与更高的复发率和更短的无复发生存期相关。MMP-9可能是预测ACTH分泌型垂体肿瘤复发的有价值工具。
