scholarly journals Features of expression of somatostatin receptors in gastric carcinomas depending on the proportion of the neuroendocrine component

2021 ◽  
Vol 67 (5) ◽  
pp. 683-686
Author(s):  
Oleg Kit ◽  
Irina Derizhanova ◽  
Nikolay Karnaukhov ◽  
Inna Novikova ◽  
Vladimir Trifanov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neuroendocrine Tumors ◽  
Neuroendocrine Carcinoma ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Receptor Status ◽  
Gastric Carcinomas ◽  
Immunohistochemical Studies ◽  
Neuroendocrine Carcinomas

In 50 patients with gastric cancer, a neuroendocrine component was screened using immunohistochemical studies with antibodies to chromogenic and synaptophysin in the surgical material, as well as a somatostatin receptor status researcher (SSTR). The neuroendocrine component in various proportions was found in 62% of observers. In 2 neuroendocrine carcinomas, expression of type 2 SSTR was observed at the level of “2+”, and only one adeno-neuroendocrine carcinoma produced the same expression. In carcinomas with and without neuroendocrine component, the expression of various types of SSTR was detected in 61.8% of observers in both neuroendocrine and exocrine structures. In the group of highly differentiated neuroendocrine tumors, 100% of the observers detected the expression of at least one of the 5 types of somatostatin receptors, and in 95% - at the «3+» level. The data obtained do not allow making statistically significant conclusions about the dependence of the expression of SSTR on the presence of the neuroendocrine component, but with the prospect of further study not only in neuroendocrine tumors, but also in exocrine and mixed carcinomas.

scholarly journals Epigenetic regulation of somatostatin and somatostatin receptors in neuroendocrine tumors and other types of cancer

2020 ◽  
Author(s):  
M.J. Klomp ◽  
S.U. Dalm ◽  
M. de Jong ◽  
R.A. Feelders ◽  
J. Hofland ◽  
...  
Keyword(s):  
Protein Expression ◽  
Neuroendocrine Tumors ◽  
Epigenetic Regulation ◽  
Somatostatin Receptors ◽  
Secretory Activity ◽  
Expression Levels ◽  
Epigenetic Machinery ◽  
Gene And Protein Expression

Abstract Both somatostatin (SST) and somatostatin receptors (SSTRs) are proteins with important functions in both physiological tissue and in tumors, particularly in neuroendocrine tumors (NETs). NETs are frequently characterized by high SSTRs expression levels. SST analogues (SSAs) that bind and activate SSTR have anti-proliferative and anti-secretory activity, thereby reducing both the growth as well as the hormonal symptoms of NETs. Moreover, the high expression levels of SSTR type-2 (SSTR2) in NETs is a powerful target for therapy with radiolabeled SSAs. Due to the important role of both SST and SSTRs, it is of great importance to elucidate the mechanisms involved in regulating their expression in NETs, as well as in other types of tumors. The field of epigenetics recently gained interest in NET research, highlighting the importance of this process in regulating the expression of gene and protein expression. In this review we will discuss the role of the epigenetic machinery in controlling the expression of both SSTRs and the neuropeptide SST. Particular attention will be given to the epigenetic regulation of these proteins in NETs, whereas the involvement of the epigenetic machinery in other types of cancer will be discussed as well. In addition, we will discuss the possibility to target enzymes involved in the epigenetic machinery to modify the expression of the SST-system, thereby possibly improving therapeutic options.

Does receptor status impact survival of patients with mid-gut neuroendocrine tumors?

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 227-227 ◽  
Author(s):  
Yi-Zarn Wang ◽  
David T Beyer
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Neuroendocrine Tumors ◽  
Statistical Significance ◽  
Somatostatin Receptors ◽  
Breast Cancer Treatment ◽  
Mibg Imaging ◽  
Term Survival ◽  
Receptor Status ◽  
Imaging Results

227 Background: Neuroendocrine tumors (NETs) are rare neoplasms increasing in incidence due to greater awareness among patients and physicians. The most reliable diagnostic imaging study has been the 111In-pentetreotide scan which binds to somatostatin receptors of the tumor. It is known that breast cancer treatment outcome is tightly correlated with degree of tumor cell differentiation and receptor status. We hypothesize that receptor status determined by 111In-pentetreotide (Octreoscan) and 123I-Metaiodobenzylguanidine (MIBG) imaging results can predict prognosis for small bowel NETs. Methods: A database with all patients seen at the LSU/Ochsner NET Program was queried for nuclear medicine scan results. Included patients had a histologically confirmed ileal, jejunal, or small intestinal NET and Octreoscan and MIBG imaging results. Kaplan-Meier survival analysis was performed and statistical significance was determined by Log-rank test (p<0.05). Results: 110 patients diagnosed between July 1994 and September 2013 were included. There were 64 females (64/110, 58%) and 46 males (46/110, 42%). Seventy-three (73/110, 66%) and sixty-three (63/100, 57%) patients had positive Octreoscan and MIBG imaging results, respectively. 5- and 10-year survival was calculated and sorted into four groups based on imaging positivity. Conclusions: Most midgut NETs present with positive Octreoscans which reflect positive receptor status; a favorable feature in prognosis based on the well-established breast cancer treatment experience. Unexpectedly, our data have shown receptor scintigraphy studies result has no baring in short term survival. More surprisingly, patients with double positive scan demonstrate a substantial survival disadvantage over a longer interval. Further longitudinal studies are required to determine if NET receptor status can reliably predict patient prognosis and the mystery of the reversal relation of the receptor status of NET patients and their prognosis. [Table: see text]

Pulmonary Neuroendocrine Carcinomas

2002 ◽  
Vol 126 (5) ◽  
pp. 545-553 ◽  
Author(s):  
Qin Huang ◽  
Alona Muzitansky ◽  
Eugene J. Mark
Keyword(s):  
Neuroendocrine Tumors ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
The Body ◽  
Low Grade ◽  
Typical Carcinoid ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

Abstract Context.—Primary pulmonary neuroendocrine tumors are traditionally classified into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC). Confusion arises frequently regarding the malignant nature of TC and the morphologic differentiation between AC and LC or SC. Objective.—To provide clinicopathologic evidence to streamline and clarify the histomorphologic criteria for this group of tumors, emphasizing the prognostic implications. Patients.—To minimize variability in diagnostic criteria and treatment plans, we analyzed a group of patients whose diagnosis and treatment occurred at a single institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and thoroughly studied 50 cases of resected tumors from 1986 to 1995. Results.—On the basis of morphologic characteristics and biologic behaviors of the tumors, we agree with many previous investigators that these tumors are all malignant and potentially aggressive. Based on our accumulated data, we have modified Gould criteria and reclassified these tumors into 5 types: (1) well-differentiated neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1 mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2) moderately differentiated neuroendocrine carcinoma (otherwise called low-grade AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise called high-grade AC) (10 cases, with more than 10 mitoses per 10 HPF and necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases, with more than 30 mitoses per 10 HPF and marked necrosis); and (5) undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well, moderately, and poorly differentiated, and undifferentiated large cell and small cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of TC in this retrospective review, a figure higher than previously recorded. Conclusion.—Using a grading system and terms comparable to those used for many years and used for neuroendocrine tumors elsewhere in the body, we found that classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly differentiated, or undifferentiated provides prognostic information and avoids misleading terms and concepts. This facilitates communication between pathologists and clinicians and thereby improves diagnosis and management of the patient.

scholarly journals Localization of Neuroendrocrine Tumors Using Somatostatin Receptor Imaging with Indium-111-Pentetreotide (OctreoScan)

1997 ◽  
Vol 4 (1) ◽  
pp. 1-3 ◽  
Author(s):  
E. Christopher Ellison ◽  
William J. Schirmer ◽  
John O. Olsen ◽  
Rodney V. Pozderac ◽  
George Hinkle ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Imaging Techniques ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Primary Tumors ◽  
Duodenal Tumor ◽  
Computed Tomography Scanning ◽  
Indium 111

Background Many imaging methods have been used to detect neuroendocrine tumors of the gastrointestinal system. There is no gold standard for identifying the location of primary tumors and their potential metastases, and most conventional imaging techniques cannot detect tumors less than 1.0 cm in size. Methods The authors have investigated the use of 111In-pentetreotide as an imaging agent for abdominal neuroendocrine tumors. Results The agent is cleared rapidly by the kidneys and is primarily excreted intact with a biologic half-life of six hours. The largest radiation burden is to the spleen and kidneys. A nine-center study conducted in Europe involved 365 patients with gastroenteropancreatic neuroendocrine tumors that were also imaged by other methods. The results of 111In-pentetreotide were in agreement with those obtained by other methods for 79% of tumor locations. An additional 110 tumor localizations were detected that were not seen with conventional methods. The smallest gastrinoma imaged by 111In-pentetreotide was a 4-mm duodenal tumor. Conclusions Scintigraphy with 111In-pentetreotide is effective in visualizing various somatostatin receptors characteristic of neuroendocrine tumors of the gastrointestinal tract. Insulinomas, however, are not well imaged. Concurrent computed tomography scanning is advised to minimize the risk of missing liver metastases.

scholarly journals Somatostatin analogues in the therapy of neuroendocrine tumors: Indications, contraindications, side-effects

2020 ◽  
Vol 74 ◽  
pp. 272-282
Author(s):  
Beata Polowczyk ◽  
Marcin Kałużny ◽  
Marek Bolanowski
Keyword(s):  
Side Effects ◽  
Neuroendocrine Tumors ◽  
Anterior Pituitary ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
In Vivo Studies ◽  
Symptomatic Therapy ◽  
Important Place ◽  
Somatostatin Receptor Ligands

The presence of somatostatin receptors (SSTRs) is crucial in planning the therapy of patients with neuroendocrine tumors. This applies especially to patients in whom surgery has proven unsuccessful or there are contraindications for it. Increased SSTR expression has been observed in many cancers originating in the neuroendocrine system. Among them we distinguish anterior pituitary adenomas producing GH in excess and leading to the development of acromegaly, adenocorticotropic adenomas that autonomously synthesize ACTH, which leads to the development of ACTH-dependent Cushing’s syndrome (Cushing’s disease), as well as adenomas of the anterior pituitary from thyrotropic cells. Rich expression of these receptors has been confirmed in epithelial tumors of neuroendocrine origin in the gastrointestinal tract, pancreas and lungs. Somatostatin analogues, also called somatostatin receptor ligands, are effective in symptomatic therapy; they enable disease control, exhibit anti-proliferative effects and allow hormonal balance, which reduces mortality among patients and improves their quality of life. The antitumor effect of somatostatin analogues has been proven in in vitro and in vivo studies. In therapy they are usually well tolerated and safe. For many years, somatostatin analogues have maintained an important place in the treatment of neuroendocrine tumors and are still the subject of many studies. The aim of the study is to analyze, based on available literature, therapeutic indications for the use of somatostatin analogues, taking into account contraindications for therapy and its possible side effects.

Whole exome sequencing and gene expression profiling of neuroendocrine carcinoma in the stomach.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 57-57
Author(s):  
Rie Makuuchi ◽  
Masanori Terashima ◽  
Masanori Tokunaga ◽  
Yutaka Tanizawa ◽  
Etsuro Bando ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Gene Expression Profiling ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Neuroendocrine Tumors ◽  
Neuroendocrine Carcinoma ◽  
Expression Profiling ◽  
Neuroendocrine Cells ◽  
Whole Exome

57 Background: Neuroendocrine carcinoma (NEC) in the stomach is a rare disease with the incidence of about 0.6 % of all gastric cancer and is well known as a highly malignant tumor with poor survival. Despite the malignant phenotype of this disease, the global gene expression profiling of gastric NEC has not yet been elucidated. We have started a comprehensive molecular profiling project that analyzes genome and transcriptome of tumor obtained from cancer patients admitted to Shizuoka Cancer Center from January 2014, setting a goal to get 3,000 samples in 3 years. We had already evaluated more than 1,500 samples from various types of malignancies, including 111 samples from gastric cancer. Here, we performed deep sequencing of 409 cancer-related genes for gastric NEC patients, adding whole-exome sequencing and gene expression profiling, to identify a gene variant of gastric NEC. Methods: Surgically-resected fresh tumor samples and peripheral blood were analyzed by whole-exome sequencing (Ion Proton, Life Technologies) and gene expression profiling (DNA microarray, Agilent Technologies). A total of 111 patients with gastric cancer were evaluated until August 2015, including 6 gastric NEC (5.4 %). We compared single nucleotide variants (SNVs) and gene expression profiles between gastric NEC and gastric adenocarcinoma. Results: All the gastric NEC patients were male with median age of 69 years (59–79 years). According to classification of TNM 7th, there were two patients with stage IA, one with IIA, one with IIIB and two with IIIC. Three of them had adenocarcinoma components constituted > 30% of the respective tumors, fulfilling the criteria for mixed adenoneuroendocrine carcinoma (MANEC), as defined by the WHO classification. There was no specific SNV for NEC. However, gene expression profiling identified several specific genes expressing in NEC; most of the highly expressed genes were also known to be expressed in neuroendocrine cells. Furthermore, CPLX2 and SCG3, which had been reported to be expressed in various neuroendocrine tumors, were included. Conclusions: Gastric NEC could be characterized by specific gene expression including those expressed in neuroendocrine cells and neuroendocrine tumors.

scholarly journals Somatostatin receptor endoradiotherapy of neuroendocrine tumors: experience in Hungarian patients

2011 ◽  
Vol 152 (10) ◽  
pp. 392-397 ◽  
Author(s):  
Péter Reismann ◽  
Zoltán Kender ◽  
Gabriella Dabasi ◽  
Lídia Sréter ◽  
Károly Rácz ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Theoretical Background ◽  
Neuroendocrine Cells ◽  
Peptide Receptor ◽  
The University

Beside conventional therapies for the treatment of neuroendocrine tumors, a new therapeutical approach, peptide receptor radionuclide therapy has been developed recently. There are two important features which make this therapy feasible: somatostatin receptors are strongly over-expressed in most neuroendocrine tumors resulting in a high tumor-to-background ratio and internalization of the somatostatin-receptor complex in neuroendocrine cells. Due to these features, neuroendocrine tumors can be treated with radiolabelled somatostatin analogues. For peptide receptor radionuclide therapy, somatostatin analogues are conjugated to a chelator that can bind a radionuclide. The most frequently used radionuclides for neuroendocrine tumor treatment are the β-emitter Yttrium-90 (90Y) and the β+γ emitter Lutetium-177 (177Lu). Candidates for somatostatin receptor endoradiotherapy are patients with progressive, metastatic, somatostatin-receptor positive neuroendocrine tumors. Many patients have been successively treated with this approach: according to international results major remission can be achieved in 25% of the cases. Although this therapy is still unavailable in Hungary, Hungarian patients can be treated with somatostatin receptor endoradiotherapy with financial support from the National Health Fund in a co-operation with the University of Basel since 2005. During the past 5 years, 51 Hungarian patients have been treated with this therapy. This review briefly summarizes the theoretical background, indications, effectiveness and side effects of somatostatin receptor endoradiotherapy and the authors present the first data obtained from Hungarian patients. Orv. Hetil., 2011, 152, 392–397.

scholarly journals Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

2021 ◽  
Vol 12 ◽  
Author(s):  
Mayank Patel ◽  
Isabel Tena ◽  
Abhishek Jha ◽  
David Taieb ◽  
Karel Pacak
Keyword(s):  
Neuroendocrine Tumors ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Rare Condition ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Well Differentiated ◽  
Succinate Dehydrogenase Subunit B

Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both “cold”, particularly octreotide and lanreotide, and “hot” analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with 68Ga-DOTATATE and 177Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in succinate dehydrogenase subunit B gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of 68Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.

scholarly journals Predictive Value of 99MTC-hynic-toc Scintigraphy in Lung Neuroendocrine Tumor Diagnosis

2019 ◽  
Vol 18 ◽  
pp. 153303381984258 ◽  
Author(s):  
Efimia Boutsikou ◽  
Konstantinos Porpodis ◽  
Vasiliki Chatzipavlidou ◽  
Georgia Hardavella ◽  
George Gerasimou ◽  
...  
Keyword(s):  
Disease Progression ◽  
Neuroendocrine Tumors ◽  
Single Photon ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Noninvasive Technique ◽  
Imaging Results ◽  
Tumors Of The Lungs

Background: Νeuroendocrine tumors of the lungs are rare arising in the thymus and gastro-entero-pancreatic tract and belonging to foregut of neuroendocrine tumors. The aim of the present prospective study was to estimate the potential impact of single-photon emission computed tomography somatostatin receptor scintigraphy using 99mTc-Tektrotyd on diagnosis, treatment response, and prognosis in patients with neuroendocrine tumors of the lungs. Methods: Thirty-six patients with neuroendocrine tumors of the lungs were evaluated by using 99mTc-HYNIC-TOC scintigraphy. The scintigraphic results were compared to liver tissue uptake (Krenning score). Likewise, the functional imaging results were compared with biochemical indices including chromogranin A, neuroendocrine-specific enolase, and insulin-like growth factor 1 at the time of diagnosis (baseline) and disease progression. Results: The number of somatostatin receptors, expressed with Krenning score, did not show any correlation with the survival of patients both at baseline ( P = .08) and at disease progression ( P = .24), and scintigraphy results did not relate significantly to progression-free survival. Comparing the results of 99mTc-HYNIC-TOC scintigraphy according to the response of patients in the initial treatment, a statistically significant negative correlation was observed both in the first and in the second scintigraphy with patients’ response ( P = .001 and P < .001, respectively). The concentrations of biochemical markers were in accordance with scintigraphy results in the diagnosis. Conclusion: This study indicates that 99mTc-HYNIC-TOC scintigraphy appears to be a reliable, noninvasive technique for detection of primary neuroendocrine tumors and their locoregional or distant metastases, although it cannot be used as a neuroendocrine tumors of the lungs predictive technique.

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