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T 盒转录因子在垂体腺瘤诊断算法中的作用。

The Role of T-box Transcription Factor in a Pituitary Adenoma Diagnostic Algorithm.

机构信息

The Department of Pathology and Laboratory Medicine, Allina Health Laboratories, Minneapolis, Minnesota (W. C. McDonald).

The Department of Geography, Macalester College, Saint Paul, Minnesota (K. N. McDonald).

出版信息

Arch Pathol Lab Med. 2021 May 1;145(5):592-598. doi: 10.5858/arpa.2020-0091-OA.

DOI:10.5858/arpa.2020-0091-OA
PMID:32991684
Abstract

CONTEXT.—: We previously examined pituitary adenomas with immunohistochemical (IHC) stains for steroidogenic factor 1, Pit-1, anterior pituitary hormones, cytokeratin CAM 5.2, and the α-subunit of human chorionic gonadotropin and found that a screening panel comprising stains for steroidogenic factor 1, Pit-1, and adrenocorticotropic hormone successfully classified most cases and reduced the overall number of stains required.

OBJECTIVES.—: To examine the potential role of IHC stain for T-box transcription factor (Tpit) in the classification of our series of pituitary adenomas and to update our screening panel as necessary.

DESIGN.—: We collected 157 pituitary adenomas from 2 institutions and included these in tissue microarrays. Immunostains for Tpit were scored in a blinded fashion using the Allred system. Adenomas were assigned to a gold standard class based on IHC pattern followed by application of available clinical and serologic information. Test characteristics were calculated. Correlation analyses, cluster analyses, and classification tree analyses were used to see whether IHC staining patterns reliably reflected adenoma class.

RESULTS.—: Of the cases collected, 147 (93.6%) had sufficient material for Tpit analysis. IHC stain for Tpit identified 8 null cell adenomas (all nonfunctioning clinically) as silent corticotrophs; Tpit stains showed better sensitivity, specificity, positive predictive value, and negative predictive value than IHC for adrenocorticotropic hormone and cytokeratin CAM 5.2. Correlation analyses continued to show the expected relationships among IHC stains. Cluster analyses showed grouping of adenomas into clinically consistent groups. Classification tree analysis underscored the central role of transcription factor IHC stains, including Tpit, in adenoma classification.

CONCLUSIONS.—: Substitution of Tpit stain for the adrenocorticotropic hormone stain improves our prior algorithm by reducing the number of false-negatives and false-positives. As a result, fewer adenomas are classified as null cell adenoma, and more adenomas are classified as silent corticotroph adenoma.

摘要

背景

我们之前使用类固醇生成因子 1(SF-1)、Pit-1、前垂体激素、细胞角蛋白 CAM 5.2 和人绒毛膜促性腺激素的 α 亚单位的免疫组织化学(IHC)染色检查了垂体腺瘤,并发现由 SF-1、Pit-1 和促肾上腺皮质激素染色组成的筛选面板成功地对大多数病例进行了分类,并减少了所需的总染色数量。

目的

检查 T 盒转录因子(Tpit)的 IHC 染色在我们系列垂体腺瘤分类中的潜在作用,并根据需要更新我们的筛选面板。

设计

我们从 2 个机构收集了 157 个垂体腺瘤,并将其纳入组织微阵列中。使用 Allred 系统以盲法对 Tpit 的免疫染色进行评分。根据免疫组化模式,将腺瘤分配到金标准类别,并应用现有的临床和血清学信息。计算测试特征。使用相关性分析、聚类分析和分类树分析,观察 IHC 染色模式是否可靠地反映腺瘤类别。

结果

在所收集的病例中,有 147 例(93.6%)有足够的 Tpit 分析材料。SF-1 染色鉴定了 8 例无功能的无功能细胞腺瘤(均为无功能性)为沉默促肾上腺皮质激素细胞;Tpit 染色的敏感性、特异性、阳性预测值和阴性预测值均优于促肾上腺皮质激素和细胞角蛋白 CAM 5.2 的 IHC 染色。相关性分析继续显示 IHC 染色之间的预期关系。聚类分析显示腺瘤形成具有临床一致性的组群。分类树分析强调了转录因子 IHC 染色(包括 Tpit)在腺瘤分类中的核心作用。

结论

用 Tpit 染色代替促肾上腺皮质激素染色可以通过减少假阴性和假阳性来改进我们之前的算法。因此,更少的腺瘤被归类为无功能细胞腺瘤,更多的腺瘤被归类为沉默促肾上腺皮质激素腺瘤。

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