Unveiling the identities of null cell tumours: Epigenomics corroborate subtle histological cues in pituitary neuroendocrine tumour/adenoma classification

被引：7

作者：

Dottermusch, Matthias ^{[1
,5
]}

Schueller, Ulrich ^{[1
,2
,3
]}

Hagel, Christian ^{[1
]}

Saeger, Wolfgang ^{[1
,4
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany

[3] Res Inst Childrens Canc Ctr Hamburg, Hamburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Inst Pathol, Hamburg, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, Martinistr 52, D-20246 Hamburg, Germany

来源：

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY | 2023年 / 49卷 / 01期

关键词：

copy number profile; DNA methylation; null cell; pituitary adenoma; pituitary neuroendocrine tumour; TRANSCRIPTION FACTORS; DIAGNOSIS; GLAND;

D O I：

10.1111/nan.12870

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

AimsPituitary neuroendocrine tumour (PitNET)/adenoma classification is based on cell lineage and requires immunopositivity for adenohypophysial hormones and/or transcription factors (TFs) steroidogenic factor 1 (SF1), T-box transcription factor TBX19 (TPIT) or pituitary-specific positive transcription factor 1 (PIT1). PitNET/adenomas lacking lineage affiliation are termed 'null cell' tumours (NCTs). NCT diagnosis may be afflicted by methodological limitations and inconsistent diagnostic approaches. Previous studies have questioned the existence of true NCTs. In this study, we explore the epigenomic identities of PitNET/adenomas lacking clear TF immunopositivity. MethodsSeventy-four hormone-negative PitNET/adenomas were immunostained and scored for SF1, TPIT and PIT1 expression. All tumours were classified as gonadotroph, corticotroph, PIT1-positive or 'null cell'. NCTs were subjected to global DNA methylation analysis. Epigenomic profiles of NCTs were compared to reference tumours using Uniform Manifold Approximation and Projection (UMAP) plotting and methylation-based classification. ResultsTF immunostaining revealed definite lineage identity in 59 of 74 (79.7%) hormone-negative PitNET/adenomas. Of the remaining 15 NCTs, 13 demonstrated minimal and inconclusive nuclear SF1 or TPIT expression (5 and 8, respectively). Two NCTs were entirely immunonegative. UMAP plotting and methylation-based classification demonstrated that the epigenomes of NCTs with minimal SF1 or TPIT expression were adequately affiliated with gonadotroph or corticotroph lineages, respectively. The two immunonegative NCTs were located near the corticotroph PitNET/adenomas via UMAP, whereas the methylation classifier could not match these two cases to predefined tumour classes. ConclusionsEpigenomic analyses substantiate lineage identification based on minimal TF immunopositivity in PitNET/adenomas. This strategy dramatically decreases the incidence of NCTs and further challenges the legitimacy of NCTs as a distinct PitNET/adenoma subtype. Our study may be useful for guiding diagnostic efforts and future considerations of PitNET/adenoma classification.

引用

页数：8