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Multilineage pituitary neuroendocrine tumors with PIT1/SF1 co-expression

ABSTRACT: Pituitary neuroendocrine tumors (PitNET)/adenomas are classified according to cell lineage, which requires immunohistochemistry for the transcription factors (TFs) PIT1, SF1, and TPIT. Co-expression of PIT1/SF1 was previously reported in PitNETs, which otherwise correspond to the somatotroph lineage. However, little is known about the clinicopathological features of these tumors. We compiled an in-house case series of 100 tumors, previously diagnosed as densely or sparsely granulated somatotroph PitNETs. Following TF staining, histopathological features associated with PIT1/SF1-coexpression were assessed. Global DNA methylation profiling was conducted on 31 of 100 in-house samples and integrated with publicly available sample data. The majority (74%, 52/70) of our densely granulated somatotroph PitNETs (DGST) unequivocally co-expressed PIT1 and SF1 (DGST-PIT1/SF1). None of our SGST (0%, 0/30) stained positive for SF1 (SGST-PIT1). Integrated molecular analyses including publicly available sample data confirmed that DGST-PIT1/SF1, DGST-PIT1 and SGST-PIT1 represent distinct tumour subtypes. In summary, we spotlight that a substantial proportion of previously diagnosed densely granulated somatotroph PitNET co-express PIT1 and SF1 and exhibit clinical, histopathological, and molecular distinctness from other pure PIT1-lineage somatotroph PitNET.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246645 | GEO | 2024/01/24

REPOSITORIES: GEO

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Project description:Background Micro RNAs (miRNAs) are a class of small non-coding RNAs that are involved in post transcriptional gene expression regulation. miRNAS can be found in various bodily fluids including plasma. Recently circulating plasma miRNAs have been studied as biomarkers in various tumors including pituitary neuroendocrine tumors (PitNETs). However the identification of PitNET derived miRNAs in plasma remains a challenging task due to tumor volume, mass and miRNA dilution within blood. To our knowledge this is the first study that has used the NGS approach to characterize circulating miRNAs in plasma acquired from Bilateral petrosal sinus sampling (BIPSS) - a gold standard in diagnosis of ACTH secreting PitNETs. Results We sequenced plasma samples that were acquired from sinistral and dextral sides of sinus petrosus inferior and complementary plasma from peripheral venous blood (PVB). BIPSS samples were collected in three separate time periods: before administration of corticotropin releasing hormone (CRH), 5 minutes after stimulation and 15 minutes after stimulation with CRH. The highest amount of differentially expressed miRNAs was observed 5 minutes after CRH stimulation (20 upregulated, 14 downregulated). During the BIPSS procedure the highest amount of ACTH was released in the sinistral side during the 5th minute after the stimulation by CRH. In the plasma of sinistral side at the 5th minute we identified two miRNAs: hsa-miR-7-5p and hsa-miR-375-3p that were highly upregulated compared to other BIPSS samples and samples from PVB. Using clustering analysis we were able to distinguish plasma samples acquired from BIPSS from PVB plasma, indicating that the miRNA fraction characterized in this study has potentially PitNET borne origin. Conclusions In this study we provided the first insight into the landscape of circulating miRNAs in close proximity to the ACTH secreting PitNET. The data indicates that ACTH secreting PitNET releases two circulating miRNAs upon stimulation with CRH (hsa-mir-7-5p, hsa-mir-375-3p) alongside with ACTH implying the further studies of these miRNA as diagnostic markers.

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Multilineage pituitary neuroendocrine tumors with PIT1/SF1 co-expression

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