Therapeutic response to pazopanib: case report and literature review on molecular abnormalities of aggressive prolactinomas.
Therapeutic response to pazopanib: case report and literature review on molecular abnormalities of aggressive prolactinomas.
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DOI：
10.3389/fendo.2023.1195792
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
侵袭性催乳素瘤（aprl）由于其高再生率和潜在的危及生命的并发症而构成了重大的临床挑战。在本研究中，我们报告了一例APRL患者，该患者接受了多种治疗方式的试验，目的是通过证实我们与先前文献的经验，对APRL的分子异常和管理进行回顾。共审阅268篇文章，纳入46篇。包括病例报告和系列，以及调查aprl分子和/或遗传分析的研究。根据欧洲内分泌学会指南，我们特别注意纳入了描述催乳素瘤属于APRL亚型的研究；然而，作者没有将肿瘤标记为“侵袭性”或“非典型”。此外，我们报告了一名56岁男性的病例报告，该病例表现为侵袭性APRL，对多种治疗方式都有耐药性。文献回顾显示aprl的多种分子异常包括ADAMTS6、MMP-9、PITX1、VEGF、POU6F2、CDKN2A和Rb基因的突变和/或失调。错配修复基因、microrna的下调以及RASSF1A、p27和MGMT等特定基因的高甲基化被发现与泌乳素瘤的侵袭性直接相关。APRL受体分析显示，雌激素受体（ER）水平低、生长抑素受体（SSTR5）和表皮生长因子受体（EGFR）水平升高与侵袭性增加和增殖活性升高有关。我们的患者PD-L1、MSH2和MSH6免疫组化染色呈阳性，而微阵列分析显示CDKN2A和POU6F2基因突变。尽管接受了两次手术切除、放疗和服用多巴胺激动剂，肿瘤仍在继续发展。患者接受了帕唑帕尼治疗，产生了积极的反应，患者在6个月内保持无进展。然而，随后的观察显示肿瘤进展。患者开始使用PD-L1抑制剂派姆单抗，但肿瘤继续进展。aprl是复杂的肿瘤，需要多学科的治疗方法。了解这些肿瘤的分子基础对于理解其发病机制和确定精准医学治疗的潜在靶点至关重要。
Aggressive prolactinomas (APRLs) pose a significant clinical challenge due to their high rate of regrowth and potentially life-threatening complications. In this study, we present a case of a patient with an APRL who had a trial of multiple therapeutic modalities with the aim to provide a review of molecular abnormalities and management of APRLs by corroborating our experience with previous literature. A total of 268 articles were reviewed and 46 were included. Case reports and series, and studies that investigated the molecular and/or genetic analysis of APRLs were included. Special care was taken to include studies describing prolactinomas that would fall under the APRL subtype according to the European Society of Endocrinology guidelines; however, the author did not label the tumor as “aggressive” or “atypical”. Addiontionally, we present a case report of a 56-year-old man presented with an invasive APRL that was resistant to multiple treatment modalities. Literature review revealed multiple molecular abnormalities of APRLs including mutations in and/or deregulation of ADAMTS6, MMP-9, PITX1, VEGF, POU6F2, CDKN2A, and Rb genes. Mismatch repair genes, downregulation of microRNAs, and hypermethylation of specific genes including RASSF1A, p27, and MGMT were found to be directly associated with the aggressiveness of prolactinomas. APRL receptor analysis showed that low levels of estrogen receptor (ER) and an increase in somatostatin receptors (SSTR5) and epidermal growth factor receptors (EGFR) were associated with increased invasiveness and higher proliferation activity. Our patient had positive immunohistochemistry staining for PD-L1, MSH2, and MSH6, while microarray analysis revealed mutations in the CDKN2A and POU6F2 genes. Despite undergoing two surgical resections, radiotherapy, and taking dopamine agonists, the tumor continued to progress. The patient was administered pazopanib, which resulted in a positive response and the patient remained progression-free for six months. However, subsequent observations revealed tumor progression. The patient was started on PD-L1 inhibitor pembrolizumab, yet the tumor continued to progress. APRLs are complex tumors that require a multidisciplinary management approach. Knowledge of the molecular underpinnings of these tumors is critical for understanding their pathogenesis and identifying potential targets for precision medical therapy.
影响因子：
2.4
作者：
Miyajima K;Takekoshi S;Itoh J;Kakimoto K;Miyakoshi T;Osamura RY
通讯作者：
Osamura RY