Overexpression of ODF1 in Gastrointestinal Tract Neuroendocrine Neoplasms: a Novel Potential Immunohistochemical Biomarker for Well-differentiated Neuroendocrine Tumors

Li, Baicheng; Li, Xinjun; Mao, Ruiqi; Liu, Min; Fu, Limei; Shi, Lei; Zhao, Songlin; Fu, Mingxia

doi:10.1007/s12022-020-09649-8

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…While there are some suggested potential biomarkers such as DLL3 and ODF1 for this distinction [72,73], the data require validation on larger studies from multiple anatomic sites. Moreover, exceptional NETs may show aberrant p53 expression [74,75].…”

Section: What Are Functional Imaging Studies In Neuroendocrine Neopla...mentioning

confidence: 99%

Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms

et al. 2022

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In this review, we detail the changes and the relevant features that are applied to neuroendocrine neoplasms (NENs) in the 2022 WHO Classification of Endocrine and Neuroendocrine Tumors. Using a question-and-answer approach, we discuss the consolidation of the nomenclature that distinguishes neuronal paragangliomas from epithelial neoplasms, which are divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The criteria for these distinctions based on differentiation are outlined. NETs are generally (but not always) graded as G1, G2, and G3 based on proliferation, whereas NECs are by definition high grade; the importance of Ki67 as a tool for classification and grading is emphasized. The clinical relevance of proper classification is explained, and the importance of hormonal function is examined, including eutopic and ectopic hormone production. The tools available to pathologists for accurate classification include the conventional biomarkers of neuroendocrine lineage and differentiation, INSM1, synaptophysin, chromogranins, and somatostatin receptors (SSTRs), but also include transcription factors that can identify the site of origin of a metastatic lesion of unknown primary site, as well as hormones, enzymes, and keratins that play a role in functional and structural correlation. The recognition of highly proliferative, well-differentiated NETs has resulted in the need for biomarkers that can distinguish these G3 NETs from NECs, including stains to determine expression of SSTRs and those that can indicate the unique molecular pathogenetic alterations that underlie the distinction, for example, global loss of RB and aberrant p53 in pancreatic NECs compared with loss of ATRX, DAXX, and menin in pancreatic NETs. Other differential diagnoses are discussed with recommendations for biomarkers that can assist in correct classification, including the distinctions between epithelial and non-epithelial NENs that have allowed reclassification of epithelial NETs in the spine, in the duodenum, and in the middle ear; the first two may be composite tumors with neuronal and glial elements, and as this feature is integral to the duodenal lesion, it is now classified as composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET). The many other aspects of differential diagnosis are detailed with recommendations for biomarkers that can distinguish NENs from nonneuroendocrine lesions that can mimic their morphology. The concepts of mixed neuroendocrine and non-neuroendocrine (MiNEN) and amphicrine tumors are clarified with information about how to approach such lesions in routine practice. Theranostic biomarkers that assist patient management are reviewed. Given the significant proportion of NENs that are associated with germline mutations that predispose to this disease, we explain the role of the pathologist in identifying precursor lesions and applying molecular immunohistochemistry to guide genetic testing.

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Section: What Are Functional Imaging Studies In Neuroendocrine Neopla...mentioning

confidence: 99%

Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms

et al. 2022

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“…We also identified the expression of SATB2 in some of these tumors. This transcription factor, originally thought to be a feature of NETs of the distal gastrointestinal tract (terminal ileum, appendix, colon, and rectum),15–17 has also been identified in middle ear NETs18 as well as Merkel cell carcinomas that are neuroendocrine carcinomas19; this work adds CENETs to the list of SATB2-positive NENs. We performed stains for T-brachyury to determine if this transcription factor that defines the midline and is expressed in the spinal column20 is relevant, but all tumors tested were negative.…”

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 98%

Cauda Equina Neuroendocrine Tumors

Sylvia

Mete

Schüller

et al. 2022

American Journal of Surgical Pathology

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The tumor formerly known as "cauda equina paraganglioma" was recently renamed as cauda equina neuroendocrine tumor (CENET) based on distinct biological and genetic properties. Nevertheless, it remains insufficiently understood. For this study, we retrieved CENETs (some previously reported), from the pathology files of 3 institutions; we examined their immunohistochemical profile, including common neuroendocrine tumor-associated hormones and transcription factors. We identified 24 CENETs from 7 female and 17 male adult patients, with a median age of 47 years. Six included neurofilament-positive ganglion cells. All tumors tested were positive for INSM1, synaptophysin, chromogranin A, SSTR2, and CD56 as well as at least 1 keratin (AE1/AE3, CAM5.2); CK7 and CK20 were negative. Glial fibrillary acidic protein was negative, except for peripheral nontumoral elements. S100 protein was variable but mainly expressed in scattered sustentacular cells. All but 1 tumor tested were positive for HOXB13; several stained for SATB2, and all tumors were consistently negative for GATA3. All tumors tested were negative for transcription factors found in various other epithelial neuroendocrine neoplasms including TTF1, CDX2, PIT1, TPIT, SF1, and PAX8; staining for T-brachyury was negative. Four of 5 CEN-ETs tested had at least focal tyrosine hydroxylase reactivity. Serotonin expression was detected in all 21 tumors tested; it was diffusely positive in 5 and had variable positivity in the remainder. A few tumors had scattered cells expressing gastrin, calcitonin, pancreatic polypeptide, and peptide YY, while glucagon, adrenocorticotropic hormone, and monoclonal carcinoembryonic antigen were negative. PSAP expression was found focally in 4 of 5 tumors examined. SDHB was consistently intact; ATRX was intact in 14 tumors and showed only focal loss in 3. The median Ki-67 labeling index was 4.5% (range: 1% to 15%). We conclude that CENET represents a distinct neuroendocrine neoplasm; the subset with ganglion cells qualifies for designation as composite gangliocytoma/neuroma-neuroendocrine tumor (CoGNET) as defined in the 2022 WHO classification of neuroendocrine neoplasms. In addition to INSM1, chromogranin, synaptophysin, and keratins, the most characteristic finding is nuclear HOXB13 expression; a subset also express SATB2. Serotonin is the most common hormone expressed. The cytogenesis and pathogenesis of these lesions remains unclear.

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“…In fact, in a survey of the Human Protein Atlas database, ODF-1 showed significant expression in neuroendocrine neoplasms. Li et al assessed gastrointestinal NENs and found that firstly, ODF-1 was positive in 83/85 (97.6%) of gastrointestinal NENs compared with neuroendocrine carcinomas 25/52 (48.1%) and secondly, protein expression displayed distinct immunohistochemical staining patterns between lower grade well differentiated neuroendocrine tumors (grades 1 and 2) and higher grade neuroendocrine neoplasms (G3 NET and NECs) [49]. The contrasting patterns of protein expression, wherein ODF-1 is perinuclear in G1 and G2 NENs and cytoplasmic or dot-like in grade 3 or NECs suggest a role in the maintenance of cell structure in NENs while the diffuse positivity in lower grade NETs imply divergence in pathogenesis to NECs.…”

Section: Odf1mentioning

confidence: 99%

Biomarkers in gastroenteropancreatic neuroendocrine neoplasms

Jacoba

Weber

2023

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of reviewGastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) represent a heterogenous group of rare tumors emanating from neuroendocrine cells that are clinically silent for prolonged periods of time without detection. Traditional biomarkers lack sufficiently high enough specificity and sensitivity for these tumors and their secreted products. New molecules are sought to improve accuracy of detection and monitoring of GEP-NENs. The purpose of this review is to highlight recent advances in the discovery of novel biomarkers and their potential characteristics and utility as markers of GEP-NENs. Recent findingsSeveral recent GEP-NEN investigations regarding NETest demonstrate superior sensitivity and specificity in diagnosis and disease monitoring as compared with chromogranin A. Among several tissue-based emergent candidate molecules as biomarkers for GEP-NEN INSM1 has demonstrated consistently excellent characteristics when compared with traditional markers including chromogranin A, synaptophysin, and CD56.

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Overexpression of ODF1 in Gastrointestinal Tract Neuroendocrine Neoplasms: a Novel Potential Immunohistochemical Biomarker for Well-differentiated Neuroendocrine Tumors

Cited by 10 publications

References 20 publications

Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms

Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms

Cauda Equina Neuroendocrine Tumors

Biomarkers in gastroenteropancreatic neuroendocrine neoplasms

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