Chinezu Laura, Gliga Maximilian Cosma, Borz Mihnea Bogdan, Gliga Camelia, Pascanu Ionela Maria
Department of Histology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania.
Department of Endocrinology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania.
J Clin Med. 2025 Apr 26;14(9):3000. doi: 10.3390/jcm14093000.
Cushing's disease (CD) is a rare disorder caused by adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumors, which lead to chronic hypercortisolism and significant complications with increased mortality. These tumors are characterized by a substantial heterogeneity in their biological behavior, prognosis, and therapeutic response, making their management challenging. While transsphenoidal surgery remains the first-line treatment, recurrence rates remain high, and alternative therapeutic approaches, such as pharmacological therapy and radiotherapy, have a variable efficacy and are frequently limited due to side effects. Increasing evidence suggests that molecular biomarkers, both immunohistochemical and genetic, may play an important role in predicting a tumor's aggressiveness, recurrence risk, and response to targeted therapies. The immunohistochemical evaluation of its granulation pattern, Ki-67 proliferation index, and E-cadherin expressions have been linked to a tumor's invasiveness and surgical outcomes, while somatostatin and dopamine receptor expressions may influence its response to Pasireotide and cabergoline therapy. Genetic alterations such as USP8 mutations impact tumor growth and its response to targeted therapies, whereas CABLES1 and TP53 alterations may contribute to more aggressive tumor behavior. Despite these findings, the clinical applicability of many of these markers remains limited by inconsistent validation and lack of standardized cutoff values. This narrative review provides an update on the latest evidence regarding the roles of molecular biomarkers in corticotropinomas, emphasizing their role in prognosis, recurrence risk, and the response to different treatment options. A better understanding and integration of these biomarkers into clinical practice could lead to a better patient stratification, more efficient therapeutic strategies, and personalized treatment approaches for patients with CD.
库欣病（CD）是一种由分泌促肾上腺皮质激素（ACTH）的垂体神经内分泌肿瘤引起的罕见疾病，可导致慢性皮质醇增多症并引发严重并发症，增加死亡率。这些肿瘤在生物学行为、预后和治疗反应方面具有显著的异质性，这使得它们的管理具有挑战性。虽然经蝶窦手术仍然是一线治疗方法，但复发率仍然很高，而其他治疗方法，如药物治疗和放射治疗，疗效不一，且常常因副作用而受到限制。越来越多的证据表明，免疫组化和基因方面的分子生物标志物可能在预测肿瘤的侵袭性、复发风险以及对靶向治疗的反应中发挥重要作用。对其颗粒模式、Ki-67增殖指数和E-钙黏蛋白表达进行免疫组化评估，已与肿瘤的侵袭性和手术结果相关联，而生长抑素和多巴胺受体表达可能会影响其对帕西瑞肽和卡麦角林治疗的反应。诸如USP8突变等基因改变会影响肿瘤生长及其对靶向治疗的反应，而CABLES1和TP53改变可能导致肿瘤行为更具侵袭性。尽管有这些发现，但许多这些标志物的临床适用性仍然受到验证不一致和缺乏标准化临界值的限制。这篇叙述性综述提供了关于分子生物标志物在促肾上腺皮质激素瘤中作用的最新证据更新，强调了它们在预后、复发风险以及对不同治疗选择的反应中的作用。更好地理解这些生物标志物并将其整合到临床实践中，可能会为库欣病患者带来更好的患者分层、更有效的治疗策略和个性化治疗方法。
