Higher ARNT expression is associated with the sparsely granulated phenotype in somatotroph pituitary adenomas: An immunohistochemical study.

IF 3.8 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Pituitary Pub Date : 2026-10-16 DOI:10.1007/s11102-026-01776-5

Cristiana Călin, Iulia Florentina Burcea, Ramona Dobre, Roxana-Ioana Dumitriu Stan, Mihai Alin Publik, Dana Cristina Terzea, Mihail-Constantin Ceaușu, Cătălina Poiană

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引用次数: 0

Abstract

Purpose: Somatotroph pituitary adenomas are a heterogeneous group comprising distinct histopathological subtypes, including the well-defined densely granulated (DG) and sparsely granulated (SG) phenotypes. While the aryl hydrocarbon receptor-interacting protein (AIP) pathway has been implicated in pituitary tumorigenesis, the role of aryl hydrocarbon receptor nuclear translocator (ARNT) in somatotroph tumors remains poorly characterized.

Methods: We retrospectively analyzed 71 surgically treated somatotroph pituitary adenomas, clinically managed in a tertiary endocrinology center between 2020 and 2025. Immunohistochemical expression of AIP, AHR and ARNT was evaluated and correlated with clinicopathological characteristics, including cytokeratin pattern, hormonal expression and Ki-67 index.

Results: Moderate/strong ARNT expression was more frequent in SG than in DG adenomas (60% vs. 17.6%, p = 0.002). Patients with moderate/strong ARNT expression were younger than those with absent/weak expression (median 39 vs. 46 years, p = 0.044). In multivariable analysis, ARNT expression remained associated with the SG phenotype after adjustment for age and sex (adjusted OR 6.84, 95% CI 2.05-22.84; p = 0.002). No significant associations were observed between ARNT expression and Ki-67 index, baseline GH or IGF1 levels, AIP/AHR immunoexpression or the evaluated clinical outcomes, including biochemical control during first-generation somatostatin receptor ligand therapy.

Conclusions: Increased ARNT expression is associated with the sparsely granulated phenotype in somatotroph pituitary adenomas, suggesting that ARNT expression may reflect tumor differentiation rather than proliferative activity. However, the present findings do not demonstrate additional prognostic or therapeutic utility beyond granulation pattern. Further molecular and transcriptomic studies are warranted to clarify the biological role of ARNT.

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高ARNT表达与生长发育型垂体腺瘤的稀疏颗粒表型相关：免疫组织化学研究。

目的：垂体生长滋长性腺瘤是由不同的组织病理学亚型组成的异质性组，包括定义明确的密集颗粒（DG）和稀疏颗粒（SG）表型。虽然芳基烃受体相互作用蛋白（AIP）途径与垂体肿瘤发生有关，但芳基烃受体核转运蛋白（ARNT）在生长发育不良肿瘤中的作用仍不清楚。方法：回顾性分析2020年至2025年在三级内分泌中心临床治疗的71例手术治疗的垂体生长滋长性腺瘤。评估AIP、AHR和ARNT的免疫组织化学表达，并与临床病理特征（包括细胞角蛋白模式、激素表达和Ki-67指数）相关。结果：中等/强烈的ARNT表达在SG中比在DG腺瘤中更常见（60% vs. 17.6%, p = 0.002）。中等/强烈ARNT表达的患者比不表达/弱表达的患者年轻（中位39岁vs. 46岁，p = 0.044）。在多变量分析中，在调整年龄和性别后，ARNT表达仍然与SG表型相关（调整OR为6.84,95% CI 2.05-22.84; p = 0.002）。未观察到ARNT表达与Ki-67指数、基线GH或IGF1水平、AIP/AHR免疫表达或评估的临床结果（包括第一代生长抑素受体配体治疗期间的生化控制）之间存在显著关联。结论：ARNT表达升高与垂体生长缺陷腺瘤的稀疏颗粒表型相关，提示ARNT表达可能反映肿瘤分化而非增殖活性。然而，目前的研究结果并不能证明除肉芽化模式外的其他预后或治疗效用。需要进一步的分子和转录组学研究来阐明ARNT的生物学作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pituitary 医学-内分泌学与代谢

CiteScore

7.10

自引率

7.90%

发文量

审稿时长

6 months

期刊介绍： Pituitary is an international publication devoted to basic and clinical aspects of the pituitary gland. It is designed to publish original, high quality research in both basic and pituitary function as well as clinical pituitary disease. The journal considers: Biology of Pituitary Tumors Mechanisms of Pituitary Hormone Secretion Regulation of Pituitary Function Prospective Clinical Studies of Pituitary Disease Critical Basic and Clinical Reviews Pituitary is directed at basic investigators, physiologists, clinical adult and pediatric endocrinologists, neurosurgeons and reproductive endocrinologists interested in the broad field of the pituitary and its disorders. The Editorial Board has been drawn from international experts in basic and clinical endocrinology. The journal offers a rapid turnaround time for review of manuscripts, and the high standard of the journal is maintained by a selective peer-review process which aims to publish only the highest quality manuscripts. Pituitary will foster the publication of creative scholarship as it pertains to the pituitary and will provide a forum for basic scientists and clinicians to publish their high quality pituitary-related work.