Differential expression of PTEN, pAKT1, pRPS6, and mismatch repair proteins in pituitary neuroendocrine tumors.

IF 3.1 3区 医学 Q1 PATHOLOGY
Mehmet Arda Inan, Melike Urganci, Berkay Simsek, Meric Coskun, Melih Sahin, Emrah Celtikci, Aylar Poyraz
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引用次数: 0

Abstract

Pituitary neuroendocrine tumors (PitNETs), formerly known as adenomas, are heterogeneous neoplasms that can result in significant clinical morbidity. The molecular pathogenesis of these tumors has been linked to mutations in genes such as GNAS, MEN1, and USP8, with their roles in tumor development well characterized. However, the potential contributions of the phosphatase and tensin homolog (PTEN) and microsatellite instability (MSI)-related genes remain insufficiently elucidated. This study aimed to investigate the immunohistochemical expression profiles of PTEN, phosphorylated protein kinase B (pAKT1), phosphorylated ribosomal protein S6 (pRPS6), and DNA mismatch repair (MMR) proteins in PitNETs. In this retrospective analysis, archived formalin-fixed, paraffin-embedded tumor samples from 154 patients were stained for PTEN, pAKT1, and pRPS6, and H-scores were calculated based on the three most intensely stained high-power fields. Additionally, MMR protein expression (PMS2, MLH1, MSH2, and MSH6) was assessed to evaluate MSI status. Gonadotroph tumors were the most common subtype (45.5%). Statistical analysis revealed a significant loss of PTEN expression in lactotroph tumors, along with a sex-based association with tumor type. Notably, pRPS6 expression was significantly elevated in tumors exhibiting PTEN loss. No cases showed loss of MMR protein expression, indicating MMR proficiency across the cohort. Our findings suggest that dysregulation of the PTEN pathway may contribute to lactotroph tumorigenesis, underscoring its potential as a therapeutic target. In contrast, despite its established role as a tumor-agnostic biomarker, MMR status does not appear to hold clinical relevance for alternative treatment strategies in PitNETs.

垂体神经内分泌肿瘤中PTEN、pAKT1、pRPS6和错配修复蛋白的差异表达
垂体神经内分泌肿瘤(PitNETs),以前称为腺瘤,是一种异质性肿瘤,可导致显著的临床发病率。这些肿瘤的分子发病机制与GNAS、MEN1和USP8等基因的突变有关,这些基因在肿瘤发展中的作用已经得到了很好的描述。然而,磷酸酶和紧张素同源物(PTEN)和微卫星不稳定性(MSI)相关基因的潜在作用尚未得到充分阐明。本研究旨在研究PTEN、磷酸化蛋白激酶B (pAKT1)、磷酸化核糖体蛋白S6 (pRPS6)和DNA错配修复(MMR)蛋白在PitNETs中的免疫组化表达谱。在这项回顾性分析中,我们对154例患者的经福尔马林固定、石蜡包埋的肿瘤标本进行PTEN、pAKT1和pRPS6染色,并根据三个染色强度最高的高倍视野计算h评分。此外,评估MMR蛋白表达(PMS2、MLH1、MSH2和MSH6)来评估MSI状态。促性腺激素肿瘤是最常见的亚型(45.5%)。统计分析显示,PTEN在嗜乳性肿瘤中的表达明显缺失,并与肿瘤类型存在性别相关性。值得注意的是,在PTEN缺失的肿瘤中,pRPS6的表达显著升高。没有病例显示MMR蛋白表达缺失,表明整个队列中MMR水平较高。我们的研究结果表明,PTEN通路的失调可能有助于嗜乳性肿瘤的发生,强调了其作为治疗靶点的潜力。相比之下,尽管MMR作为肿瘤不可知生物标志物的作用已经确立,但在PitNETs中,MMR状态似乎与替代治疗策略没有临床相关性。
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来源期刊
Virchows Archiv
Virchows Archiv 医学-病理学
CiteScore
7.40
自引率
2.90%
发文量
204
审稿时长
4-8 weeks
期刊介绍: Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
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