scholarly journals Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin

2020 ◽  
Vol 31 (4) ◽  
pp. 401-410
Author(s):  
Carl Christofer Juhlin ◽  
Jan Zedenius ◽  
Anders Höög
Keyword(s):  
Second Generation ◽  
Neuroendocrine Differentiation ◽  
Diagnostic Process ◽  
Neuroendocrine Neoplasms ◽  
Clinical Routine ◽  
Who Grade ◽  
Primary Tumors ◽  
Tissue Specific ◽  
Neuroendocrine Markers ◽  
Immunohistochemical Markers

AbstractNeuroendocrine neoplasms (NENs) have traditionally been identified via expression of proteins associated to the regulation of secretory vesicles and granules. We report the clinical usage of the “second-generation” proteins ISL LIM homeobox 1 (ISL1), INSM transcriptional repressor 1 (INSM1), and secretagogin (SECG) as immunohistochemical markers of neuroendocrine differentiation since their introduction in clinical routine and compare the results with the established proteins chromogranin A (CGA) and synaptophysin (SYP). In total, 161 tumors, including 139 NENs and 22 “non-NENs” (unrelated tumors with an initial suspicion of NEN), were informatively stained for ISL1, and subsets were also interrogated for INSM1 and/or SECG. Diffuse or focal positive immunoreactivity was noted for ISL1 in 91/139 NENs (65%) and in 6/22 (27%) non-NENs, for INSM1 in 76/85 NENs (89%) and in 2/5 (40%) non-NENs, and for SECG in 49 out of 64 NENs (77%) and in 0/5 non-NENs (0%). Generally, ISL1, INSM1, and SECG exhibited sensitivities in line with or slightly below that of CGA and SYP—largely attributable to tissue-specific patterns regarding tumoral origin. Moreover, for pancreatic and small intestinal NENs, the two largest subgroups, ISL1 staining results were consistent irrespectively of tumor source and WHO grade. We verify previously suggested immunohistochemical schemes of neuroendocrine markers of first- and second-generations to facilitate the diagnostic process for NENs and confirm that the second-generation neuroendocrine markers display tissue-specific patterns. We therefore recommend their implementation in tertiary endocrine pathology centers, not least to aid in the identification of primary tumors when analyzing metastases.

scholarly journals INSM1 Is a Highly Specific Marker of Neuroendocrine Differentiation in Primary Neoplasms of the Gastrointestinal Tract, Appendix, and Pancreas

2020 ◽  
Vol 153 (6) ◽  
pp. 811-820 ◽  
Author(s):  
Kelsey E McHugh ◽  
Sanjay Mukhopadhyay ◽  
Erika E Doxtader ◽  
Christopher Lanigan ◽  
Daniela S Allende
Keyword(s):  
Goblet Cell ◽  
Neuroendocrine Differentiation ◽  
Neuroendocrine Neoplasms ◽  
Specific Marker ◽  
Low Grade ◽  
Ki 67 ◽  
Neuroendocrine Markers ◽  
Primary Neoplasms ◽  
Poorly Differentiated ◽  
Well Differentiated

Abstract Objectives INSM1 has been described as a sensitive and specific neuroendocrine marker. This study aims to compare INSM1 with traditional neuroendocrine markers in gastrointestinal neuroendocrine neoplasms. Methods Retrospective review (2008-2018) was used to retrieve paraffin-embedded tissue from 110 gastrointestinal neuroendocrine neoplasms and controls that was subsequently stained with INSM1, synaptophysin, chromogranin, CD56, and Ki-67. Results INSM1 was positive in 16 of 17 (94.1%) gastric, 17 of 18 (94.4%) pancreatic, 13 of 18 (72.2%) small bowel, 17 of 21 (81.0%) colonic, and 26 of 36 (72.2%) appendiceal tumors. INSM1 was positive in 58 of 70 (82.9%) well-differentiated neuroendocrine tumors, 17 of 20 (85.0%) poorly differentiated neuroendocrine carcinomas, 8 of 11 (72.7%) low-grade goblet cell adenocarcinomas (grade 1), and 6 of 9 (66.7%) high-grade goblet cell adenocarcinomas (grade 2/3). INSM1 sensitivity for neuroendocrine neoplasms (80.9%) was less than that of synaptophysin (99.1%), chromogranin (88%), and CD56 (95.3%); specificity was higher (95.7% vs 86.0%, 87.3%, and 86.0%, respectively). Conclusions INSM1 is a useful marker of neuroendocrine differentiation in gastrointestinal neuroendocrine and mixed neuroendocrine neoplasms. Compared with traditional neuroendocrine markers, INSM1 is less sensitive but more specific.

scholarly journals WHO Grade 2 Neuroendocrine Tumor in a 15-Year-Old Male: A Case Report and Literature Review

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Eric Johannesen ◽  
Van Nguyen
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Neuroendocrine Differentiation ◽  
Failure To Thrive ◽  
Proliferation Index ◽  
Neuroendocrine Neoplasms ◽  
Who Grade ◽  
Increased Risk ◽  
History Of ◽  
Well Differentiated

Neuroendocrine tumors, distinguished from adenocarcinomas by their neuroendocrine differentiation, are the most common pediatric epithelial malignancy that most often occurs in the appendix. In 2010, the WHO classified neuroendocrine neoplasms into three grades based on morphology, mitotic count, and Ki67 proliferation index. A 15-year-old male with a history of anemia and failure to thrive was diagnosed with a well-differentiated neuroendocrine tumor in the jejunum that invaded into the subserosal soft tissue and metastasized to four lymph nodes. Pediatric neuroendocrine tumors frequently arise within hereditary tumor syndromes with pancreatic neuroendocrine tumors being the most common. Several studies also indicate an elevated risk of small intestinal neuroendocrine tumors in which children born to a parent with a history of neuroendocrine tumors in the small intestine have a significant increased risk of developing one.

scholarly journals Second-Generation Neuroendocrine Immunohistochemical Markers: Reflections from Clinical Implementation

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 874
Author(s):  
Carl Christofer Juhlin
Keyword(s):  
Neuroendocrine Tumors ◽  
Second Generation ◽  
Neuroendocrine Differentiation ◽  
Clinical Experiences ◽  
Clinical Implementation ◽  
Immunohistochemical Markers ◽  
Metastatic Lesions ◽  
Poorly Differentiated ◽  
Focal Expression ◽  
Neuroendocrine Carcinomas

When analyzing tumors by histopathology, endocrine pathologists have traditionally been restricted to a few key immunohistochemical markers related to secretory vesicles in order to pinpoint neuroendocrine differentiation—most notably Chromogranin A (CGA) and Synaptophysin (SYP). Although proven of great clinical utility, these markers sometimes exhibit tissue-specific patterns depending on tumor origin, and non-neuroendocrine tumors might sometimes display focal expression. Moreover, CGA and SYP might be partially or totally absent in highly proliferative neuroendocrine carcinomas, making the diagnosis particularly challenging on small biopsies of metastatic lesions with unknown location of the primary tumor. The advent of second-generation neuroendocrine markers ISL LIM Homeobox 1 (ISL1), INSM Transcriptional Repressor 1 (INSM1) and Secretagogin (SECG) have expanded the pathology toolbox considerably, constituting markers that often retain expression even in poorly differentiated neuroendocrine carcinomas. As non-neuroendocrine tumors seldom express these antigens, the specificity of ISL1, INSM1 and SECG make them welcome additions to clinical practice. In this commentary, recent advances of this field as well as initial clinical experiences from a tertiary neuroendocrine center are discussed.

Cytokeratin 7 and 20 as immunohistochemical markers in identification of primary tumors in craniospinal metastases: Do they have a significant role?

2003 ◽  
Vol 23 (4) ◽  
pp. 271-274 ◽  
Author(s):  
Mana Taweevisit ◽  
Putchong Isarakul ◽  
Mookda Chaipipat ◽  
Kanista Keetacheeva ◽  
Vannee Wattanasirmkit ◽  
...  
Keyword(s):  
Significant Role ◽  
Cytokeratin 7 ◽  
Primary Tumors ◽  
Immunohistochemical Markers

CASE STUDY ON CIRCUMSCRIBED GLIOMAS, THEIR CLINICOPATHOLOGICAL CORRELATION IN A TERTIARY CARE CENTER

2021 ◽  
pp. 42-45
Author(s):  
Esther Alffi Papang ◽  
K. Rama
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tertiary Care ◽  
Biological Behavior ◽  
Low Grade ◽  
Lower Grade ◽  
Who Grade ◽  
Primary Tumors ◽  
Short Period ◽  
The Impact

The histogenesis and biological behavior of primary tumors of the central nervous system(CNS) are very diverse. The majority of present gliomas as benign, slow growing lesions classied as by the WHO classicati grade I or II (Low grade gliomas) on of CNS tumors. However, a signicant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classied as WHO grade III or IV(High grade gliomas). Astrocytomas are primary central nervous system tumours that can develop in adults or in children. They arise from the Astrocytes. They can be divided into diffuse that generally have a higher grade and poorer prognosis and those that are localised that tend to be of a lower grade and have a better prognosis. In this study, we outline the basic histological spectrum and features, epidemiological aspects and grade of circumscribed gliomas (localised) or other Astrocytic tumours according to WHO classication . These are the Pilocytic Astrocytoma, Pilomyxoid Astrocytoma, Subependymal giant cell Astrocytoma, Pleomorphic xanthoastrocytoma and Anaplastic astrocytoma . The knowledge of these tumours are important as they are one of the commonest cause of mortality and morbidity in both the young and old, accounting for about 60% of the glial tumours. Therefore neuropathological diagnosis and tumour characteristics will therefore profoundly inuence the impact of treatment strategies.

scholarly journals Update Regarding Imaging of Neuroendocrine Neoplasms

2019 ◽  
Vol 192 (02) ◽  
pp. 171-182
Author(s):  
Jens Holger Figiel ◽  
Simon G. Viniol ◽  
Jannis Görlach ◽  
Anja Rinke ◽  
Damiano Librizzi ◽  
...  
Keyword(s):  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
Primary Tumors ◽  
Advantages And Disadvantages ◽  
Key Points ◽  
Wide Range ◽  
Small Primary ◽  
Noninvasive Therapy ◽  
Spectrum Of Indications

Background Neuroendocrine neoplasms (NEN) are a heterogeneous group of tumors characterized by the expression of typical proteins. A wide range of morphological and functional imaging methods is required in order to adequately assess the course of the disease and to optimally treat the patient. The spectrum of indications ranges from the detection of small primary tumors to the documentation of the metastasis pattern and the assessment of the suitability for certain invasive or noninvasive therapy methods. The exact recording and quantification of findings is indispensable. Methods This article is based on a comprehensive literature search on the different aspects of neuroendocrine neoplasm imaging. Results This article is intended to provide an overview of the available imaging procedures with their respective advantages and disadvantages for diagnostics and their value for the follow-up of neuroendocrine neoplasms. Recommendations for examination protocols, typical image findings, and an outlook regarding future developments are presented. Key Points:  Citation Format

scholarly journals N-cadherin increases after androgen deprivation and is associated with metastasis in prostate cancer

2010 ◽  
Vol 17 (2) ◽  
pp. 469-479 ◽  
Author(s):  
Karin Jennbacken ◽  
Tajana Tešan ◽  
Wanzhong Wang ◽  
Heléne Gustavsson ◽  
Jan-Erik Damber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Neuroendocrine Differentiation ◽  
Hormonal Treatment ◽  
Androgen Deprivation ◽  
Prostate Tumors ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Molecular Alterations

Androgen-deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. One factor that has been implicated in the metastatic process is the cell adhesion molecule N-cadherin. In this study, we investigated if the expression of N-cadherin was influenced by androgen deprivation and was associated with metastasis in prostate cancer. The effect of androgen deprivation on N-cadherin expression was initially studied in androgen-dependent (AD) LNCaP and androgen-independent (AI) LNCaP-19 and PC-3 prostate cancer cell lines. Expression of N-cadherin increased in the absence of androgens in AI LNCaP-19 primary tumors and metastases and also in vitro, but not in AI PC-3 tumors, indicating a possible involvement of the androgen receptor in the regulation of N-cadherin. N-cadherin was absent in AD LNCaP tumors. No clear associations between N-cadherin and factors related with epithelial–mesenchymal transition or neuroendocrine differentiation could be established. In addition, N-cadherin was evaluated by immunohistochemistry in human prostate tumors. Expression of N-cadherin was more frequently found in tumors from patients treated with ADT than in tumors from patients with no prior hormonal treatment. N-cadherin expression was also associated with metastasis and Gleason score. Furthermore, increased N-cadherin was detected in prostate cancer biopsies already 3 months after initiation of ADT when tumors were in a regressed state. In summary the results indicate that androgen deprivation induces N-cadherin in prostate tumors. Moreover, N-cadherin was increased in castration-resistant tumors in patients with established metastases. This might indicate that castration induces molecular alterations in the tumor cells, resulting in a more invasive and metastatic phenotype.

scholarly journals The value of neuroendocrine markers for response to therapy and survival in patients with advanced non-small cell lung cancer

2010 ◽  
Vol 138 (1-2) ◽  
pp. 37-42
Author(s):  
Marina Petrovic ◽  
Nevenka Ilic ◽  
Dejan Baskic
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Response ◽  
Neuroendocrine Differentiation ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Neuroendocrine Markers

Introduction. Non-small cell lung cancer (NSCLC) accounts for about 70-80% of all lung cancers. In comparison with small cell lung cancer, NSCLC has relatively low therapy response. Discovery of neuroendocrine markers within the NSCLC group (10-30%) has initiated the issue of their importance in the therapy and prognosis. Objective. The aim of this study was to determine the influence of neuroendocrine differentiation on treatment response and survival in patients with advanced NSCLC. Methods. A clinical trial included 236 patients (73.7% males), with diagnosis of NSCLC, determined by histological verification. These patients were treated by combined chemo- and X-ray therapy at stage III (without pleural effusion) or chemotherapy only at stage III (with pleural effusion) and stage IV of NSCLC. When the progression had been noted at the stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron-specific enolase (NSE), chromogranin A (ChrA) as well as synapthophysin (SYN) expression in tissue examples was determined by immunohistochemical analysis with monoclonal mouse anti human bodies (DAKO Comp, Denmark). The treatment was conducted during 4 to 6 chemotherapeutic cycles. The efficacy was assessed after the therapy regimen; median survival time was assessed after the randomization. Results. NSE, ChrA and SYN expression were noted in 56 (23.7%), 33 (13.9%) and 39 (16.5%) patients, respectively. Better therapeutic response was significantly higher in patients with expression of NSE, ChrA and SYN (p<0.05). There was significant correlation between therapy response and the percentage of positive tumour cells with neuroendocrine differentiation (p<0.05). The one-year and two-year follow-up survival period in patients with neuroendocrine expression was 64% (without expression 28%; p<0.001) and 30% (p=0.000). Conclusion. Tissue expression of neuroendocrine markers influences greatly a therapeutic response in patients with advanced stage of NSCLC. Better therapeutic response was recorded in patients with positive expression of neuroendocrine markers and higher percentage of positive tumour cells. Median survival time is higher in patients in III or IV stage of NSCLC, when neuroendocrine markers are expressed.

scholarly journals The Expression of Chromogranin A, Syanptophysin and Ki67 in Detecting Neuroendocrine Neoplasma at High Grade Colorectal Adenocarcinoma

2021 ◽  
Vol 9 (A) ◽  
pp. 1142-1147
Author(s):  
W. A. Gusti Deasy ◽  
M. Husni Cangara ◽  
Andi Alfian Zainuddin ◽  
Djumadi Achmad ◽  
Syarifuddin Wahid ◽  
...  
Keyword(s):  
Chromogranin A ◽  
Colorectal Adenocarcinoma ◽  
Final Diagnosis ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
Neuroendocrine Markers ◽  
Study Results ◽  
Cell Neoplasm ◽  
Sample Characteristics

BACKGROUND: Neuroendocrine neoplasm (NEN) is an epithelial cell neoplasm that can give a histopathological appearance resembling high-grade colorectal adenocarcinoma. Immunohistochemical assays with specific neuroendocrine markers of chromogranin A and synaptophysin are required to establish a definite diagnosis of NEN. AIM: This study aimed to determine whether there was an expression of chromogranin A, synaptophysin and Ki67 which indicated the presence of neuroendocrine neoplasms in samples that have been diagnosed as high-grade colorectal adenocarcinoma. MATERIALS AND METHODS: A study of the expression of chromogranin A, synaptophysin and Ki67 in paraffin blocks was carried out as a result of biopsy and tissue surgery of 70 samples of colorectal tumor specimens diagnosed with colorectal adenocarcinoma. Descriptive analyses were used to assess the study results of the amount of chromogranin A, synaptophysin, and sample characteristics. RESULTS: We discovered that eight (8) samples (11.4%) were NEN from 70 previously diagnosed samples as high-grade colorectal adenocarcinoma using immunohistochemical assay with neuroendocrine markers, namely chromogranin A and synaptophysin. CONCLUSION: The final diagnosis obtained from 8 samples diagnosed as NEN were Neuroendocrine tumor (NET) G1, G2, and G3, respectively 1.4% and LCNEC 7.1% based on the specific neuroendocrine markers of chromogranin A, synaptophysin and Ki67.

scholarly journals The effect of the extent of neuroendocrine differentiation on cytopathological findings in primary neuroendocrine neoplasms of the breast

2021 ◽  
Vol 38 (4) ◽  
pp. 216
Author(s):  
CananKelten Talu ◽  
Burcu Guzelbey ◽  
Ezgi Hacihasanoglu ◽  
Yasemin Cakir ◽  
MehmetA Nazli
Keyword(s):  
Neuroendocrine Differentiation ◽  
Neuroendocrine Neoplasms
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